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Original Articles
Lipid Metabolism Related Gene ACSL3 as a Biomarker for Predicting Immunotherapy Outcomes in Lung Adenocarcinoma
Taiping He, Jinhan Hu, Haoyue Guo, Meng Diao, Yuanyuan Wang, Yuhan Wu, Lei Cheng, Chao Zhao, Xuefei Li, Caicun Zhou
Received November 22, 2024  Accepted January 16, 2025  Published online January 20, 2025  
DOI: https://doi.org/10.4143/crt.2024.1119    [Accepted]
AbstractAbstract PDF
Purpose
Investigate the role of lipid metabolism in the tumor immune microenvironment (TIME) of lung adenocarcinoma (LUAD) and identify vital lipid metabolism-related genes (LMRGs) that contribute to immunotherapy outcomes.
Materials and Methods
1130 LUAD patients were acquired utilizing public databases. Multiple algorithms were used to analyze the contribution of lipid metabolism in TIME. Importantly, cell lines, clinical samples (52 patients in surgery cohort and 36 in immunotherapy cohort), animal models, RNA-seq, experiments in protein and mRNA levels were conducted for identifying and validating key biomarker in LUAD immunotherapy.
Results
A prognostic signature comprising 33 LMRGs was developed and validated as an effective predictor of prognosis and TIME, with a C-index of 0.766 (95% CI: 0.729-0.804). Additionally, we identified Acyl-CoA Synthetase Long Chain Family Member 3 (ACSL3) as a potential biomarker for immunotherapy prognosis. The expression of ACSL3 was verified in 88 clinical tissues from LUAD patients, which indicated that elevated ACSL3 expression was correlated with worse progression-free survival (PFS) (p<0.001) and overall survival (OS) (p=0.008). Subsequent experiments revealed that knockdown of ACSL3 in vivo enhanced the efficacy of immunotherapy, potentially through increasing interferon α secretion, as indicated by Bulk RNA-seq and ELISA analysis, thereby promoting the infiltration of anti-tumor immune cells.
Conclusion
The study established a model that accurately predicts immunotherapy response, prognosis, and TIME dynamics in LUAD patients. Notably, the pivotal role of ACSL3 in driving tumor progression and immune evasion was uncovered, offering novel insights into the optimization of immunotherapy strategies for LUAD.
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Long-Term Survival Outcomes of Surgical Resection for Lung Adenocarcinoma with Intraoperatively Diagnosed Pleural Metastasis: Target Treatment Era
Yelee Kwon, Jae Kwang Yun, Geun Dong Lee, Se Hoon Choi, Yong-Hee Kim, Hyeong Ryul Kim
Received October 15, 2024  Accepted December 27, 2024  Published online December 30, 2024  
DOI: https://doi.org/10.4143/crt.2024.993    [Accepted]
AbstractAbstract PDF
Purpose
This study aimed to evaluate the clinical impact of main tumor resection on long-term survival compared with pleural biopsy alone in patients with lung adenocarcinoma who were intraoperatively diagnosed with pleural metastasis.
Materials and Methods
A total of 176 patients with adenocarcinoma who had unexpected pleural metastasis detected during surgery from 2002 to 2021 were retrospectively analyzed. Each surgeon decided whether to perform main tumor resection or pleural biopsy alone.
Results
The patients were grouped based on the surgical approaches: main tumor resection (Resection group; n=83) and pleural biopsy only (O&C group; n=93). The Resection group had better overall survival (OS, 10-year survival: 27.9% vs. 9.4%; median survival: 68.3 vs. 36.6 months; p<0.01) and locoregional progression-free survival (10-year survival: 12.5% vs. 7.1%; median survival: 19.6 vs. 10.6 months; p<0.01) than the O&C group. Similar results were found for OS in patients who received tyrosine kinase inhibitors (TKIs) as first-line therapy (10-year survival: 49.2% vs. 15.0%; median survival: 72.2 vs. 45.4 months; p=0.03), patients who did not undergo TKIs treatment (10-year survival: 29.4% vs. 9.2%; median survival: 82.4 vs. 23.8 months; p<0.01), and patients with positive target gene mutation (10-year survival: 31.7% vs. 10.1%; median survival: 72.2 vs. 33.7 months; p<0.01). In multivariate analysis, pleural biopsy only (hazard ratio, 1.73; p=0.04) was a significant predictor of OS.
Conclusion
Main tumor resection can improve survival in patients with lung adenocarcinoma who had unexpected pleural metastasis during operation.
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Predictive Value of the nProfiler 1 Assay for the Efficacy of Adjuvant S-1–Based Doublet Chemotherapy in Stage III Gastric Cancer: A Post-Hoc Analysis of a Randomized Phase III Trial
Dong Ki Lee, Choong-kun Lee, Hyo Song Kim, Sun Jin Sym, Dae Young Zang, Ki Hyang Kim, Joo Han Lim, Hae Su Kim, Kyung Hee Lee, Heon Yung Gee, Sun Young Rha, Hyunki Kim, Minkyu Jung
Received July 25, 2024  Accepted November 9, 2024  Published online November 12, 2024  
DOI: https://doi.org/10.4143/crt.2024.705    [Epub ahead of print]
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The nProfiler 1 Stomach Cancer Assay (nProfiler1), designed to predict responses to fluorouracil-based adjuvant chemotherapy, measures the expression of four gastric cancer target genes (GZMB, WARS, SFRP4, and CDX1). The randomized phase III POST trial aimed to compare the efficacies of two adjuvant S-1-based doublet chemotherapies: S-1 plus cisplatin (SP) and S-1 plus docetaxel (DS). This study aimed to validate the nProfiler1 assay using a distinct cohort from the POST trial.
Materials and Methods
The nProfiler1 assay stratifies patients into three groups (low-risk, intermediate-risk, and high-risk) using the prognostic single-patient classifier and two groups (chemotherapy-benefit and no-benefit) using the predictive single-patient classifier. The nProfiler1 assay was applied to formalin-fixed paraffin-embedded slides obtained from the POST trial. Disease-free survival (DFS) and overall survival (OS), including 5-year survival rates, were calculated for the enrolled patients.
Results
Of the 153 patients in the POST trial, 118 were included in the post-hoc analysis. With a median follow-up of 57.9 months, no significant difference in DFS or OS was observed between the SP and DS groups. The prognostic single-patient classifier predicted the OS in the SP group (p=0.043) but not in the DS group (p=0.594). The chemotherapy-benefit group exhibited numerically longer DFS than the no-benefit group in the SP and DS groups.
Conclusion
The nProfiler1 assay offers valuable insights into the prognosis and efficacy of adjuvant chemotherapy based on fluorouracil plus platinum doublet regimens but not docetaxel-containing regimens. Further validation with larger patient cohorts and different regimens is warranted.
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Genitourinary cancer
Clear Cell Adenocarcinoma of Urethra: Clinical and Pathologic Implications and Characterization of Molecular Aberrations
Boram Song, Seok Hyun Lee, Jeong Hwan Park, Kyung Chul Moon
Cancer Res Treat. 2024;56(1):280-293.   Published online September 11, 2023
DOI: https://doi.org/10.4143/crt.2023.577
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
This study aimed to evaluate the molecular features of clear cell adenocarcinoma (CCA) of the urinary tract and investigate its pathogenic pathways and possible actionable targets.
Materials and Methods
We retrospectively collected the data of patients with CCA between January 1999 and December 2016; the data were independently reviewed by two pathologists. We selected five cases of urinary CCA, based on the clinicopathological features. We analyzed these five cases by whole exome sequencing (WES) and subsequent bioinformatics analyses to determine the mutational spectrum and possible pathogenic pathways.
Results
All patients were female with a median age of 62 years. All tumors were located in the urethra and showed aggressive behavior with disease progression. WES revealed several genetic alterations, including driver gene mutations (AMER1, ARID1A, CHD4, KMT2D, KRAS, PBRM1, and PIK3R1) and mutations in other important genes with tumor-suppressive and oncogenic roles (CSMD3, KEAP1, SMARCA4, and CACNA1D). We suggest putative pathogenic pathways (chromatin remodeling pathway, mitogen-activated protein kinase signaling pathway, phosphoinositide 3-kinase/AKT/mammalian target of rapamycin pathway, and Wnt/β-catenin pathway) as candidates for targeted therapies.
Conclusion
Our findings shed light on the molecular background of this extremely rare tumor with poor prognosis and can help improve treatment options.

Citations

Citations to this article as recorded by  
  • Urethral clear cell adenocarcinoma in an adult female: A rare case report
    Yacob Sheiferawe Seman, Michael Teklehaimanot Abera, Fadil Nuredin Abrar, Tesfaye Kebede Legesse, Mesfin Asefa Tola, Tsiyon Nigusie Alemu
    Urology Case Reports.2025; 58: 102882.     CrossRef
  • Two rare cases of primary clear cell adenocarcinoma of the urethra: clinical experience, case report and literature review
    Bohao Jiang, Jiyuan Hu, Benqiao Wang, Xujia Liu, Ling Tong, Yitong Xu, Hao Zhang
    Frontiers in Oncology.2025;[Epub]     CrossRef
  • Association between CACNA1D polymorphisms and hypospadias in a southern Chinese population
    Ye He, Binyao Li, Xinying Zhao, Lingling Pan, Yanqing Liu, Chaoting Lan, Fuming Deng, Wen Fu, Yan Zhang, Xiaoyu Zuo
    Journal of Pediatric Urology.2024; 20(3): 438.e1.     CrossRef
  • The L‐type calcium channel CaV1.3: A potential target for cancer therapy
    Xuerun Liu, Boqiang Shen, Jingyi Zhou, Juan Hao, Jianliu Wang
    Journal of Cellular and Molecular Medicine.2024;[Epub]     CrossRef
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Lung and Thoracic cancer
Aggressive Local Ablative Radiotherapy Mitigates Progression Risk in Oligometastatic Lung Adenocarcinoma
Gowoon Yang, Kyung Hwan Kim, Chang Geol Lee, Min Hee Hong, Hye Ryun Kim, Yeona Cho, Hong In Yoon
Cancer Res Treat. 2024;56(1):115-124.   Published online August 29, 2023
DOI: https://doi.org/10.4143/crt.2023.600
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
This study aimed to determine the role of local ablative radiotherapy (LART) in oligometastatic/oligoprogressive lung adenocarcinoma.
Materials and Methods
Patients (n=176) with oligometastatic lung adenocarcinoma treated with LART were identified, and those treated with LART at the initial diagnosis of synchronous oligometastatic disease (OMD group) or treated with LART when they presented with repeat oligoprogression (OPD group) were included.
Results
In the OMD group (n=54), the 1- and 3-year progression-free survival (PFS) were 50.9% and 22.5%, respectively, whereas the 1- and 3-year overall survival in the OPD group were 75.9% and 58.1%, respectively. Forty-one patients (75.9%) received LART at all gross disease sites. Tyrosine kinase inhibitor (TKI) use and all-metastatic site LART were significant predictors of higher PFS (p=0.018 and p=0.046, respectively). In patients treated with TKIs at the time of LART (n=23) and those treated with all-metastatic site LART, the 1-year PFS was 86.7%, while that of patients not treated with all-metastatic site LART was 37.5% (p=0.006). In the OPD group (n=122), 67.2% of the patients (n=82) maintained a systemic therapy regimen after LART. The cumulative incidence of changing systemic therapy was 39.6%, 62.9%, and 78.5% at 6 months, 1 year, and 2 years after LART, respectively.
Conclusion
Aggressive LART can be an option to improve survival in patients with oligometastatic disease. Patients with synchronous oligometastatic disease receiving TKI and all-metastatic site LART may have improved PFS. In patients with repeat oligoprogression, LART might potentially extend survival by delaying the need to change the systemic treatment regimen.
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Clinical Impact of Genomic and Pathway Alterations in Stage I EGFR-Mutant Lung Adenocarcinoma
Jae Seok Lee, Eun Kyung Kim, Kyung A Kim, Hyo Sup Shim
Cancer Res Treat. 2024;56(1):104-114.   Published online July 24, 2023
DOI: https://doi.org/10.4143/crt.2023.728
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
We investigated the clinical impact of genomic and pathway alterations in stage I epidermal growth factor receptor (EGFR)–mutant lung adenocarcinomas, which have a high recurrence rate despite complete surgical resection.
Materials and Methods
Out of the initial cohort of 257 patients with completely resected stage I EGFR-mutant lung adenocarcinoma, tumor samples from 105 patients were subjected to analysis using large-panel next-generation sequencing. We analyzed 11 canonical oncogenic pathways and determined the number of pathway alterations (NPA). Survival analyses were performed based on co-occurring alterations and NPA in three patient groups: all patients, patients with International Association for the Study of Lung Cancer (IASLC) pathology grade 2, and patients with recurrent tumors treated with EGFR–tyrosine kinase inhibitor (TKI).
Results
In the univariate analysis, pathological stage, IASLC grade, TP53 mutation, NPA, phosphoinositide 3-kinase pathway, p53 pathway, and cell cycle pathway exhibited significant associations with worse recurrence-free survival (RFS). Moreover, RPS6KB1 or EGFR amplifications were linked to a poorer RFS. Multivariate analysis revealed that pathologic stage, IASLC grade, and cell cycle pathway alteration were independent poor prognostic factors for RFS (p=0.002, p < 0.001, and p=0.006, respectively). In the grade 2 subgroup, higher NPA was independently associated with worse RFS (p=0.003). Additionally, in patients with recurrence treated with EGFR-TKIs, co-occurring TP53 mutations were linked to shorter progression-free survival (p=0.025).
Conclusion
Genomic and pathway alterations, particularly cell cycle alterations, high NPA, and TP53 mutations, were associated with worse clinical outcomes in stage I EGFR-mutant lung adenocarcinoma. These findings may have implications for risk stratification and the development of new therapeutic strategies in early-stage EGFR-mutant lung cancer patients.

Citations

Citations to this article as recorded by  
  • Stage-specific efficacy of osimertinib in treatment-naïve EGFR-mutant non-small cell lung cancer according to baseline genetic alterations in circulating tumor DNA
    Yoshihiko Taniguchi, Akihiro Tamiya, Mitsuo Osuga, Shun-ichi Isa, Keiichi Nakamura, Yasuyuki Mizumori, Tsutomu Shinohara, Hidetoshi Yanai, Katsumi Nakatomi, Masahide Oki, Masahide Mori, Tomohito Kuwako, Koji Yamazaki, Masahiro Shimada, Masahiko Ando, Yasu
    Investigational New Drugs.2025;[Epub]     CrossRef
  • A Novel CLTC::RPS6KB1 Fusion in a Poorly Differentiated Carcinoma Involving the Lung and Mediastinum
    Mitchell Zhao, Nicholas Protopsaltis, Mina Sabet, Shulei Sun, Grace Lin, Farnaz Hasteh, Wei Song
    International Journal of Surgical Pathology.2025;[Epub]     CrossRef
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Gastrointestinal cancer
Prevalence and Risk Factors of Germline Pathogenic Variants in Pancreatic Ductal Adenocarcinoma
Kum Hei Ryu, Sunhwa Park, Jung Won Chun, Eunhae Cho, Jongmun Choi, Dong-Eun Lee, Hyoeun Shim, Yun-Hee Kim, Sung-Sik Han, Sang-Jae Park, Sang Myung Woo, Sun-Young Kong
Cancer Res Treat. 2023;55(4):1303-1312.   Published online April 3, 2023
DOI: https://doi.org/10.4143/crt.2023.291
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The genetic attribution for pancreatic ductal adenocarcinoma (PDAC) has been reported as 5%-10%. However, the incidence of germline pathogenic variants (PVs) in Korean PDAC patients has not been thoroughly investigated. Therefore, we studied to identify the risk factors and prevalence of PV for future treatment strategies in PDAC.
Materials and Methods
Total of 300 (155 male) patients with a median age of 65 years (range, 33 to 90 years) were enrolled in National Cancer Center in Korea. Cancer predisposition genes, clinicopathologic characteristics, and family history of cancer were analyzed.
Results
PVs were detected in 20 patients (6.7%, median age 65) in ATM (n=7, 31.8%), BRCA1 (n=3, 13.6%), BRCA2 (n=3), and RAD51D (n=3). Each one patient showed TP53, PALB2, PMS2, RAD50, MSH3, and SPINK1 PV. Among them, two likely PVs were in ATM and RAD51D, respectively. Family history of various types of cancer including pancreatic cancer (n=4) were found in 12 patients. Three patients with ATM PVs and a patient with three germline PVs (BRCA2, MSH3, and RAD51D) had first-degree relatives with pancreatic cancer. Familial pancreatic cancer history and PVs detection had a significant association (4/20, 20% vs. 16/264, 5.7%; p=0.035).
Conclusion
Our study demonstrated that germline PVs in ATM, BRCA1, BRCA2, and RAD51D are most frequent in Korean PDAC patients and it is comparable to those of different ethnic groups. Although this study did not show guidelines for germline predisposition gene testing in patients with PDAC in Korea, it would be emphasized the need for germline testing for all PDAC patients.

Citations

Citations to this article as recorded by  
  • FOXM1 promotes malignant biological behavior and metabolic reprogramming by targeting SPINK1 in hepatocellular carcinoma and affecting the p53 pathway
    Xu Ding, Jinjun Shi, Zhengqing Lei, Guoqing Wang, Chenchun Fu, Xiangyu Su, Guangyu Zhu
    Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease.2025; 1871(3): 167673.     CrossRef
  • Mutant KRAS and GATA6 Stratify Survival in Patients Treated with Chemotherapy for Pancreatic Adenocarcinoma: A Prospective Cohort Study
    Jung Won Chun, Dong-eun Lee, Nayoung Han, SooBeen Heo, Hyeji Kim, Mi Rim Lee, Hyeong Min Park, Sung-Sik Han, Sang-Jae Park, Tae Hyun Kim, Woo Jin Lee, Yun-Hee Kim, Sun-Young Kong, Sang Myung Woo
    Cancers.2025; 17(5): 896.     CrossRef
  • MLH1 Inhibits Metastatic Potential of Pancreatic Ductal Adenocarcinoma via Downregulation of GPRC5C
    Wen-Jing Liu, Jun Lu, Wei-Xun Zhou, Jian-Zhou Liu, Li Zhou
    Laboratory Investigation.2024; 104(9): 102107.     CrossRef
  • Clinical Significance of PALB2 Pathogenic Germline Variant
    Min-Chae Kang, R.N., Jong Eun Park, Mi-Ae Jang, Dongju Won, Boyoung Park, Seeyoun Lee, Dong Ock Lee, Kum Hei Ryu, Yoon-Jung Chang, Sun-Young Kong
    Laboratory Medicine Online.2024; 14(4): 311.     CrossRef
  • Prevalence Estimation of the PALB2 Germline Variant in East Asians and Koreans through Population Database Analysis
    Jong Eun Park, Min-Chae Kang, Taeheon Lee, Eun Hye Cho, Mi-Ae Jang, Dongju Won, Boyoung Park, Chang-Seok Ki, Sun-Young Kong
    Cancers.2024; 16(19): 3318.     CrossRef
  • Understanding the Genetic Landscape of Pancreatic Ductal Adenocarcinoma to Support Personalized Medicine: A Systematic Review
    Antonino Pantaleo, Giovanna Forte, Candida Fasano, Martina Lepore Signorile, Paola Sanese, Katia De Marco, Elisabetta Di Nicola, Marialaura Latrofa, Valentina Grossi, Vittoria Disciglio, Cristiano Simone
    Cancers.2023; 16(1): 56.     CrossRef
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Survival Benefit of Adjuvant Chemotherapy in Patients with Pancreatic Ductal Adenocarcinoma Who Underwent Surgery Following Neoadjuvant FOLFIRINOX
So Heun Lee, Dae Wook Hwang, Changhoon Yoo, Kyu-pyo Kim, Sora Kang, Jae Ho Jeong, Dongwook Oh, Tae Jun Song, Sang Soo Lee, Do Hyun Park, Dong Wan Seo, Jin-hong Park, Ki Byung Song, Jae Hoon Lee, Woohyung Lee, Yejong Park, Bong Jun Kwak, Heung-Moon Chang, Baek-Yeol Ryoo, Song Cheol Kim
Cancer Res Treat. 2023;55(3):956-968.   Published online February 27, 2023
DOI: https://doi.org/10.4143/crt.2022.409
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The benefit of adjuvant chemotherapy following curative-intent surgery in pancreatic ductal adenocarcinoma (PDAC) patients who had received neoadjuvant FOLFIRINOX is unclear. This study aimed to assess the survival benefit of adjuvant chemotherapy in this patient population.
Materials and Methods
This retrospective study included 218 patients with localized non-metastatic PDAC who received neoadjuvant FOLFIRINOX and underwent curative-intent surgery (R0 or R1) between January 2017 and December 2020. The association of adjuvant chemotherapy with disease-free survival (DFS) and overall survival (OS) was evaluated in overall patients and in the propensity score matched (PSM) cohort. Subgroup analysis was conducted according to the pathology-proven lymph node status.
Results
Adjuvant chemotherapy was administered to 149 patients (68.3%). In the overall cohort, the adjuvant chemotherapy group had significantly improved DFS and OS compared to the observation group (DFS: median, 13.8 months [95% confidence interval (CI), 11.0 to 19.1] vs. 8.2 months [95% CI, 6.5 to 12.0]; p < 0.001; and OS: median, 38.0 months [95% CI, 32.2 to not assessable] vs. 25.7 months [95% CI, 18.3 to not assessable]; p=0.005). In the PSM cohort of 57 matched pairs of patients, DFS and OS were better in the adjuvant chemotherapy group than in the observation group (p < 0.001 and p=0.038, respectively). In the multivariate analysis, adjuvant chemotherapy was a significant favorable prognostic factor (vs. observation; DFS: hazard ratio [HR], 0.51 [95% CI, 0.36 to 0.71; p < 0.001]; OS: HR, 0.45 [95% CI, 0.29 to 0.71; p < 0.001]).
Conclusion
Among PDAC patients who underwent surgery following neoadjuvant FOLFIRINOX, adjuvant chemotherapy may be associated with improved survival. Randomized studies should be conducted to validate this finding.

Citations

Citations to this article as recorded by  
  • The survival effect of neoadjuvant therapy and neoadjuvant plus adjuvant therapy on pancreatic ductal adenocarcinoma patients with different TNM stages: a propensity score matching analysis based on the SEER database
    Hao Hu, Yang Xu, Qiang Zhang, Yuan Gao, Zhenyu Wu
    Expert Review of Anticancer Therapy.2024; 24(6): 467.     CrossRef
  • Neoadjuvant treatment of pancreatic ductal adenocarcinoma: Whom, when and how
    Nebojsa Manojlovic, Goran Savic, Stevan Manojlovic
    World Journal of Gastrointestinal Surgery.2024; 16(5): 1223.     CrossRef
  • Case Study on Analysing the Early Disease Detection of Pancreatic Ductal Adenocarcinoma in Korean Association for Clinical Oncology
    Sijithra Ponnarassery Chandran, N. Santhi
    American Journal of Clinical Oncology.2024; 47(10): 475.     CrossRef
  • Evaluating the benefits of adjuvant chemotherapy in patients with pancreatic cancer undergoing radical pancreatectomy after neoadjuvant therapy—a systematic review and meta-analysis
    Jiahao Wu, Yike Zhang, Haodong Wang, Wenyi Guo, Chengqing Li, Yichen Yu, Han Liu, Feng Li, Lei Wang, Jianwei Xu
    Frontiers in Oncology.2024;[Epub]     CrossRef
  • Prognostic factors in localized pancreatic ductal adenocarcinoma after neoadjuvant therapy and resection: a systematic review and meta-analysis
    Ammar A Javed, Alyssar Habib, Omar Mahmud, Asad Saulat Fatimi, Mahip Grewal, Nabiha Mughal, Jin He, Christopher L Wolfgang, Lois Daamen, Marc G Besselink
    JNCI: Journal of the National Cancer Institute.2024;[Epub]     CrossRef
  • 5,555 View
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Lung and Thoracic cancer
Selection Strategies and Practical Application of BRAF V600E-Mutated Non–Small Cell Lung Carcinoma
Inwoo Hwang, Yoon-La Choi, Hyunwoo Lee, Soohyun Hwang, Boram Lee, Hobin Yang, Chaithanya Chelakkot, Joungho Han
Cancer Res Treat. 2022;54(3):782-792.   Published online November 23, 2021
DOI: https://doi.org/10.4143/crt.2021.843
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The incidence of BRAF V600E mutation in non-small cell lung carcinoma (NSCLC) is lower than 2%, which poses difficulties in finding legitimate patients for targeted therapy. We investigated the predictive factors pertaining to BRAF V600E and the effectiveness of the VE1 antibody as a screening method for patient selection.
Materials and Methods
The study was designed into two steps. In a first group, BRAF-mutated NSCLCs were identified from sequencing data to determine the features of BRAF V600E mutation. The results of the first group helped the collection of adenocarcinomas with a papillary or micropapillary pattern but without EGFR or ALK alterations as a second group so that the frequency of BRAF V600E mutation could be calculated. The sensitivity and specificity of the VE1 were compared with BRAF V600E status.
Results
Among 39 BRAF-mutated NSCLCs in the first group, 20 (51%) were V600E. BRAF V600E mutation was more common in female patients and showed no significant correlation with smoking status. Nineteen cases were adenocarcinomas without EGFR and ALK alterations. The most common patterns of invasion were papillary and micropapillary along with central fibrosis. The sensitivity and specificity of the VE1 were 90.0% and 92.3%, respectively. In the second group, 6.7% of cases were VE1-positive, indicating that the prevalence was significantly higher than that reported in previous studies (0.3-1.8%).
Conclusion
BRAF V600E-mutated NSCLCs could be enriched with the application of clinicopathologic parameters, which are not perfect. Therefore, additional VE1 immunohistochemistry may be useful as a screening method.

Citations

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  • The rapidly changing field of predictive biomarkers of non-small cell lung cancer
    László József Tóth, Attila Mokánszki, Gábor Méhes
    Pathology and Oncology Research.2024;[Epub]     CrossRef
  • BRAF V600E Mutation of Non-Small Cell Lung Cancer in Korean Patients
    Hyo Yeong Ahn, Chang Hun Lee, Min Ki Lee, Jung Seop Eom, Yeon Joo Jeong, Yeong Dae Kim, Jeong Su Cho, Jonggeun Lee, So Jeong Lee, Dong Hoon Shin, Ahrong Kim
    Medicina.2023; 59(6): 1085.     CrossRef
  • The Impact of Liquid Biopsies Positive for EGFR Mutations on Overall Survival in Non-Small Cell Lung Cancer Patients
    Jonnathan Roldan Ruiz, Marta Fuentes Gago, Luis Chinchilla Tabora, Idalia Gonzalez Morais, José Sayagués, Mar Abad Hernández, Maria Cordovilla Pérez, Maria Ludeña de la Cruz, Edel del Barco Morillo, Marta Rodriguez Gonzalez
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  • Usefulness of BRAF VE1 immunohistochemistry in non–small cell lung cancers: a multi-institutional study by 15 pathologists in Korea
    Sunhee Chang, Yoon-La Choi, Hyo Sup Shim, Geon Kook Lee, Seung Yeon Ha
    Journal of Pathology and Translational Medicine.2022; 56(6): 334.     CrossRef
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Histologic Changes in Non–Small Cell Lung Cancer under Various Treatments: A Comparison of Histology and Mutation Status in Serial Samples
Chang Gok Woo, Seung-Myoung Son, Ho-Chang Lee, Hye Sook Han, Ki Hyeong Lee, Dohun Kim, Eung-Gook Kim, Ok-Jun Lee
Cancer Res Treat. 2022;54(3):737-743.   Published online September 24, 2021
DOI: https://doi.org/10.4143/crt.2021.773
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Histologic change is a resistant mechanism in lung cancer. The most common histological change is the switch from adenocarcinoma (AdenoCa) to small cell carcinoma (SCC) against to tyrosine kinase inhibitors (TKI). However, it is not clear whether other treatment modalities are involved in the histologic changes.
Materials and Methods
We investigated histological changes in eight cases, after various treatments, and compared the molecular profiles between primary tumors and changed tumors using exome sequencing where tissue was available.
Results
Three cases of AdenoCa that were changed into SCC retained the initial mutations after TKI and/or surgical treatment. After treatment with TKI and immunotherapy, an EGFR (epidermal growth factor receptor)-mutant AdenoCa changed to squamous cell carcinoma (SqCa). SqCa in a patient treated with surgery was changed into combined AdenoCa and SqCa. These two cases showed the same genetic variations between the two distinct non–small cell carcinomas (NSCC). Three patients experienced two histologic changes, which the changed tumors returned to its original subtype or changed to a combined tumor after treatments. Four cases showed combined histology in the first or second change.
Conclusion
The histology of NSCC can be changed to a single pattern or combined subtypes after various treatment modalities, and the phenotypic changes seem not fixed. Therefore, additional morphologic changes may occur regardless of their genetic status and types of treatments. To refine the new treatment strategy, consecutive repeated biopsies in progressive disease or recurrent tumor are necessary.

Citations

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  • Patients outcomes in lung adenocarcinoma transforming to small-cell lung cancer after tyrosine kinase inhibitor therapy
    Shuai Wang, Yongsen Wang, Xuan Wu, Li Yang, Xiaoju Zhang
    World Journal of Surgical Oncology.2025;[Epub]     CrossRef
  • Clinicopathologic features of histologic transformation in lung adenocarcinoma after treatment with epidermal growth factor receptor-tyrosine kinase inhibitors
    Halim Song, Deokhoon Kim, Se Jin Jang, Hee Sang Hwang, Joon Seon Song
    Annals of Diagnostic Pathology.2025; 77: 152478.     CrossRef
  • Whole Exome Sequencing Study Identifies Distinct Characteristics of Transformed Small Cell Lung Cancer With EGFR Mutation Compared to De Novo Small Cell and Primary Non‐Small Cell Lung Cancers
    Jinjing Tan, Dan Zhao, Qunhui Wang, Yanjing Peng, Jie Li, Xi Li, Nanying Che, Ying Hu, Hua Zheng
    Cancer Medicine.2025;[Epub]     CrossRef
  • Clinical application of microwave ablation combined with coaxial needle biopsy using different sequences for treating lung nodules suggestive of malignancy
    Yibing Li, Xinyou Su, Ruobing Li, Jianqiang Zhao, Aimei Ouyang, Taiyang Zuo
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    Shuo Li, Wenyuan Li, Bin Liu, Kostyantyn Krysan, Steven M. Dubinett
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    Alessandro Bonis, Andrea Dell’Amore, Vincenzo Verzeletti, Luca Melan, Giovanni Zambello, Chiara Nardocci, Giovanni Maria Comacchio, Federica Pezzuto, Fiorella Calabrese, Federico Rea
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    Taesung Jeon, Uk Jeen Oh, Jaeyoung Min, Chungyeul Kim
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    Jeong Yun Jang, Su Ssan Kim, Si Yeol Song, Young Seob Shin, Sei Won Lee, Wonjun Ji, Chang-Min Choi, Eun Kyung Choi
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    Sharia Hernandez, Rossana Lazcano, Alejandra Serrano, Steven Powell, Larissa Kostousov, Jay Mehta, Khaja Khan, Wei Lu, Luisa M. Solis
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The Clinical Outcomes of Different First-Line EGFR-TKIs Plus Bevacizumab in Advanced EGFR-Mutant Lung Adenocarcinoma
Yen-Hsiang Huang, Kuo-Hsuan Hsu, Chun-Shih Chin, Jeng-Sen Tseng, Tsung-Ying Yang, Kun-Chieh Chen, Kang-Yi Su, Sung-Liang Yu, Jeremy J.W. Chen, Gee-Chen Chang
Cancer Res Treat. 2022;54(2):434-444.   Published online August 2, 2021
DOI: https://doi.org/10.4143/crt.2021.671
AbstractAbstract PDFPubReaderePub
Purpose
The aim of this study was to investigate the efficacy of various epidermal growth factor receptor (EGFR)–tyrosine kinase inhibitors (TKIs) plus bevacizumab in advanced EGFR-mutant lung adenocarcinoma patients.
Materials and Methods
From August 2016 to October 2020, we enrolled advanced lung adenocarcinoma patients harboring exon 19 deletion or L858R receiving gefitinib, erlotinib and afatinib plus bevacizumab as the first-line treatment for the purposes of analysis.
Results
A total of 36 patients were included in the final analysis. Three patients received gefitinib, 17 received erlotinib, and 16 received afatinib combined with bevacizumab as the first-line treatment. The objective response rate was 77.8%, and disease control rate was 94.4%. The overall median progression-free survival (PFS) was 16.4 months, while the median PFS was 17.1 months in patients with exon 19 deletion, and 16.2 months in patients with L858R mutation (p=0.311). Regarding the use of different EGFR-TKIs, the median PFS was 17.1 months in the erlotinib group and 21.6 months in the afatinib group (p=0.617). In patients with brain metastasis at baseline, the median PFS was 18.9 months in the erlotinib group and 16.4 months in the afatinib group (p=0.747). Amongst patients harboring exon 19 deletion, the median PFS was 16.2 months in the erlotinib group and not-reached in the afatinib group (p=0.141). In patients with L858R mutation, the median PFS was 18.9 months in the erlotinib group and 16.2 months in the afatinib group (p=0.481).
Conclusion
Our research demonstrates that not only erlotinib combined with bevacizumab, but also afatinib plus bevacizumab as first-line treatment, provides solid clinical efficacy in advanced EGFR-mutant lung adenocarcinoma patients.

Citations

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    Yung-Hung Luo, Kung-Hao Liang, Hsu-Ching Huang, Chia-I Shen, Chi-Lu Chiang, Mong-Lien Wang, Shih-Hwa Chiou, Yuh-Min Chen
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Case Report
A Case of Simultaneously Diagnosed Lung Adenocarcinoma and Endobronchial Inflammatory Myofibroblastic Tumor with Two Distinct Types of ALK Translocation
Shikang Zhao, Wei Liu, Shuo Li, Tao Shi, Qiusong Chen, Qi Li, Leina Sun, Dian Ren, Zuoqing Song, Chun Huang, Song Xu
Cancer Res Treat. 2021;53(2):601-606.   Published online October 21, 2020
DOI: https://doi.org/10.4143/crt.2020.952
AbstractAbstract PDFPubReaderePub
A 61-year-old male patient was simultaneously diagnosed with lung adenocarcinoma and inflammatory myofibroblastic tumor (IMT). The lung adenocarcinoma and IMT harbored two distinct types of ALK translocation, LOC101927285-ALK, and TPM3-ALK, respectively. The ALK Ventana showed strong positivity on both lesions. The patient was therefore given an endobronchial cryotherapy and ALK inhibitor crizotinib. The tumors showed durable response however the left lung adenocarcinoma relapsed at 17th month post-crizotinib treatment. Tissue re-biopsy on the resistant tumor revealed an ALK exon 23 C1156Y missense mutation in addition to LOC101927285-ALK mutation. Further RNA-based sequence uncovered that the noncoding region rearrangement is the fusion mutation of EML4-ALK. The patient was therefore received alectinib, and the tumor exhibited partly response. Overall, it is very rare that two types of pulmonary tumors exist in one patient driven by two distinct ALK fusions, which emphasizes the necessity of gene sequencing in clinical decision-making and individualized therapy.

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    Meijin Huang, Xiangqing Zhu, Wenmang Xu, Jun Zhu, Xin Xun, Bin Su, Hong Chen
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    Wei Li, Meng-chen Li, Zi-xuan Fan, Zi-chen Cao, Jie Yang, Xu-dong Yang, Xiao-feng Huang
    BMC Oral Health.2025;[Epub]     CrossRef
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    Vito Longo, Francesco Pesola, Rosanna Lacalamita, Annamaria Catino, Michele Montrone, Ilaria Marech, Pamela Pizzutilo, Elisabetta Sara Montagna, Stefania Tommasi, Domenico Galetta
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    Jessica Reyes‐Angel, Louis B. Rapkin, Jeffrey P. Simons, Hiren Muzumdar
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    Yan Xiang, Shiyu Zhang, Xiaoxu Fang, Yingying Jiang, Tingwen Fang, Jinwen Liu, Kaihua Lu
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    Jinchun Wu, Yongbin Hu, Omar Abdihamid, Gengwen Huang, Sheng Xiao, Bin Li
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Original Articles
Lung cancer
Genetic Alterations in Preinvasive Lung Synchronous Lesions
Soyeon Ahn, Jisun Lim, Soo Young Park, Hyojin Kim, Hyun Jung Kwon, Yeon Bi Han, Choon-Taek Lee, Sukki Cho, Jin-Haeng Chung
Cancer Res Treat. 2020;52(4):1120-1134.   Published online June 5, 2020
DOI: https://doi.org/10.4143/crt.2020.307
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Despite advances in treatment, lung cancer remains the leading cause of cancer mortality. This study aimed to characterise genome-wide tumorigenesis events and to understand the hypothesis of the multistep carcinogenesis of lung adenocarcinoma (LUAD)
Materials and Methods
We conducted multiregion whole-exome sequencing of LUAD with synchronous atypical adenomatous hyperplasia (AAH), adenocarcinoma in situ, or minimally invasive adenocarcinoma of 19 samples from three patients to characterize genome-wide tumorigenesis events and validate the hypothesis of the multistep carcinogenesis of LUAD. We identified potential pathogenic mutations preserved in preinvasive lesions and supplemented the finding by allelic variant level from RNA sequencing.
Results
Overall, independent mutational profiles were observed per patient and between patients. Some shared mutations including epidermal growth factor receptor (EGFR , p.L858R) were present across synchronous lesions.
Conclusion
Here, we show that there are driver gene mutations in AAH, and they may exacerbate as a sequence in a histological continuum, supporting the Darwinian evolution model of cancer genome. The intertumoral and intratumoral heterogeneity of synchronous LUAD implies that multi-biomarker strategies might be necessary for appropriate treatment.

Citations

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  • Gene Expression Profiles of Multiple Synchronous Lesions in Lung Adenocarcinoma
    Jisun Lim, Yeon Bi Han, Soo Young Park, Soyeon Ahn, Hyojin Kim, Hyun Jung Kwon, Choon-Taek Lee, Sukki Cho, Jin-Haeng Chung
    Cells.2021; 10(12): 3484.     CrossRef
  • 8,818 View
  • 154 Download
  • 2 Web of Science
  • 1 Crossref
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Clinical Characteristics of Clear Cell Ovarian Cancer: A Retrospective Multicenter Experience of 308 Patients in South Korea
Hee Yeon Lee, Ji Hyung Hong, Jae Ho Byun, Hee-Jun Kim, Sun Kyung Baek, Jin Young Kim, Ki Hyang Kim, Jina Yun, Jung A Kim, Kwonoh Park, Hyo Jin Lee, Jung Lim Lee, Young-Woong Won, Il Hwan Kim, Woo Kyun Bae, Kyong Hwa Park, Der-Sheng Sun, Suee Lee, Min-Young Lee, Guk Jin Lee, Sook Hee Hong, Yun Hwa Jung, Ho Jung An
Cancer Res Treat. 2020;52(1):277-283.   Published online July 12, 2019
DOI: https://doi.org/10.4143/crt.2019.292
AbstractAbstract PDFPubReaderePub
Purpose
The purpose of this study was to evaluate clinical characteristics and treatment pattern of ovarian clear cell carcinoma (OCCC) in Korea and the role of adjuvant chemotherapy in early stage.
Materials and Methods
Medical records of 308 cases of from 21 institutions were reviewed and data including age, performance status, endometriosis, thromboembolism, stage, cancer antigen 125, treatment, recurrence, and death were collected.
Results
Regarding stage of OCCC, it was stage I in 194 (63.6%), stage II in 34 (11.1%), stage III in 66 (21.6%), and stage IV in 11 (3.6%) patients. All patients underwent surgery. Optimal surgery (residual disease ≤ 1 cm) was achieved in 89.3%. Majority of patients (80.5%) received postoperative chemotherapy. The most common regimen was taxane-platinum combination (96%). Median relapse-free survival (RFS) was 138.5 months for stage I, 33.4 for stage II, 19.3 for stage III, and 9.7 for stage IV. Median overall survival (OS) were not reached, 112.4, 48.7, and 18.3 months for stage I, II, III, and IV, respectively. Early-stage (stage I), endometriosis, and optimal debulking were identified as favorable prognostic factors for RFS. Early-stage and optimal debulking were also favorable prognostic factors for OS. Majority of patients with early-stage received adjuvant chemotherapy. However, additional survival benefit was not found in terms of recurrence.
Conclusion
Majority of patients had early-stage and received postoperative chemotherapy regardless of stage. Early-stage and optimal debulking were identified as favorable prognostic factors. In stage IA or IB, adding adjuvant chemotherapy did not show difference in survival. Further study focusing on OCCC is required.

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  • Ovarian clear cell carcinoma: open questions on the management and treatment algorithm
    Roberta Rosso, Margherita Turinetto, Fulvio Borella, Nicolas Chopin, Pierre Meeus, Alexandra Lainè, Isabelle Ray-Coquard, Olivia Le Saux, Domenico Ferraioli
    The Oncologist.2025;[Epub]     CrossRef
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    Zesi Liu, Chunli Jing, Fandou Kong
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    Daichi Kodama, Motoki Takenaka, Chiemi Saigo, Masako Azuma, Yuki Hanamatsu, Masanori Isobe, Tamotsu Takeuchi
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    Mengqi Huang, Li Ling, Yanbo Liu, Yujuan Li
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    Li Shuqing, Zhu Zhiling
    Cancer Medicine.2023; 12(6): 6668.     CrossRef
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    Hamidreza Didar, Farah Farzaneh, Hanieh Najafiarab, Kosar Namakin, Kimiya Gohari, Ali Sheidaei, Sepehr Ramezani
    Current Medical Research and Opinion.2023; 39(6): 901.     CrossRef
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    Yuan Zhuang, Hua Yang
    Cancer Control.2023;[Epub]     CrossRef
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    Satoe Fujiwara
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    Yoo-Na Kim, Yun Soo Chung, Ji Hyun Lee, Eunhyang Park, Seung-Tae Lee, Sunghoon Kim, Jung-Yun Lee
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    Yang Gao, Wei Ding, Pengpeng Qu
    Clinical and Experimental Obstetrics & Gynecology.2023;[Epub]     CrossRef
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    Aglaja De Pauw, Eline Naert, Koen Van de Vijver, Tummers Philippe, Katrien Vandecasteele, Hannelore Denys
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    Anastasios Tranoulis, Felicia Helena Buruiana, Bindiya Gupta, Audrey Kwong, Aarti Lakhiani, Jason Yap, Janos Balega, Kavita Singh
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    Peng Chen, Chi-Yuan Zhang
    Frontiers in Oncology.2022;[Epub]     CrossRef
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    Caner ÇAKIR, Fatih KILIÇ, Çiğdem KILIÇ, Dilek YÜKSEL, Vakkas KORKMAZ, Günsu KİMYON CÖMERT, Osman TÜRKMEN, Taner TURAN
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Pediatric Adenocarcinoma in Korea: A Multicenter Study
Hee-Beom Yang, Jung-Man Namgoong, Ki Hoon Kim, Dae Yeon Kim, Jinyoung Park, Hyun Beak Shin, Joong Kee Youn, Sanghoon Lee, Ji Won Lee, Sung Eun Jung, Jae Hee Chung, Yun-Mee Choe, Tae Gil Heo, In Geol Ho, Hyun-Young Kim
Cancer Res Treat. 2020;52(1):117-127.   Published online June 3, 2019
DOI: https://doi.org/10.4143/crt.2019.092
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Adenocarcinoma is an extremely rare malignancy in the pediatric population. Research regarding pediatric adenocarcinoma is very rare in Korea. This study aimed to investigate the clinical features of pediatric adenocarcinomas of various primary organ sites in Korea.
Materials and Methods
Pediatric patients under 18 years, diagnosed with adenocarcinoma of various sites between January 1995 and December 2016, were included. We retrospectively reviewed patient and tumor characteristics and calculated survival estimates, reported as 5-year survival rate and 95% confidence interval.
Results
Of 80 patients (median age, 15 years; range, 10 to 17 years), 37 (46.3%) were men, and 24 (30%) had a family history of cancer or underlying disease relevant to malignancy. The cancer locations were the colon and rectum (n=32), ovaries (n=18), stomach (n=15), lung (n=4), small bowel (n=1), and other sites (n=10). Totally, 54.8% patients (42/77) had stage 3 or 4 disease. The median follow-up period was 2.0 years (range, 0 to 20.4). The 5-year overall survival estimate for all patients, and for those with stomach, colorectal, ovarian, and other cancer sites were 57.9%±11.5%, 58.2%±25.7%, 41.5%±18.2%, 87.5%±16.2%, and 64.0%±34.4%, respectively. The 5-year survival rate differed significantly between categories of adenocarcinomas into gastrointestinal (GI) (44.7%) and non-GI adenocarcinomas (78.8%) (p=0.007). The 5-year survival rate also differed significantly according to carcinoembryonic antigen level (69.3% in < 3 ng/mL, 23.8% in > 3 ng/mL; p < 0.001).
Conclusion
In pediatric patients, adenocarcinomas arise from various organs and are often diagnosed at advanced stages. Large, prospective studies for their accurate clinical characteristics and prognostic factors are needed.

Citations

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  • Pretreatment level of circulating tumor cells is associated with lymph node metastasis in papillary thyroid carcinoma patients with ≤ 55 years old
    Ming Yu, Jiaqin Deng, Yihua Gu, Yeqian Lai, Yuedong Wang
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    Luisella Righi, Alberto Righi, Simona Vatrano, Ida Rapa, Angela Listì, Jasna Metovic, Michele Rocca, Mariacristina Salone, Paolo Giovenali, Angelo Sidoni, Fabrizio Tabbò, Angelo Paolo Dei Tos, Marco Volante, Mauro Papotti
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Impact of Pulmonary Tuberculosis on the EGFR Mutational Status and Clinical Outcome in Patients with Lung Adenocarcinoma
In Kyoung Hwang, Seung Sook Paik, Seung Hyeun Lee
Cancer Res Treat. 2019;51(1):158-168.   Published online April 2, 2018
DOI: https://doi.org/10.4143/crt.2018.084
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Although it has been suggested that pulmonary tuberculosis (TB) is associated with increased risk of lung cancer, the exact mechanism is not clearly identified. We investigated the effect of pulmonary TB on the epidermal growth factor receptor (EGFR) mutational status and clinical outcome in patients with pulmonary adenocarcinoma.
Materials and Methods
We reviewed data of patients diagnosed with pulmonary adenocarcinoma harboring EGFR mutations and treated at our institution from 2008 to 2015. We divided our population into two groups: patients with pre-existing TB lesions on chest computed tomography scan (TB group) and those without the lesions (non-TB group). We compared the differences in EGFR mutational status, response to tyrosine kinase inhibitors (TKIs) and survival between the two groups.
Results
A total of 477 patients with pulmonary adenocarcinoma were analyzed. One hundred eighty-three patients (39%) had EGFR-mutated tumors and 100 (21%) patients had pre-existing TB lesions. The frequency of EGFR mutation was significantly higher in the TB group compared with the non-TB group (56% vs. 34%, p=0.038). Pre-existing TB lesions were independently associated with more frequent EGFR mutations in multivariate analysis (odds ratio, 1.43). In addition, both the progression-free survival (9.1 months vs. 11.6 months, p=0.020) and the overall survival (19.4 months vs. 24.5 months, p=0.014) after first-line EGFR-TKIs were significantly shorter in the TB group than in the non-TB group.
Conclusion
Previous pulmonary TB may be associated with more frequent EGFR mutations and poorer treatment response to EGFR-TKIs in patients with pulmonary adenocarcinoma.

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  • A DNA Methylation Signature From Buccal Swabs to Identify Tuberculosis Infection
    Lovisa Karlsson, Isabelle Öhrnberg, Shumaila Sayyab, David Martínez-Enguita, Mika Gustafsson, Patricia Espinoza, Melissa Méndez-Aranda, Cesar Ugarte-Gil, Lameck Diero, Ronald Tonui, Jakob Paues, Maria Lerm
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Incremental Role of Pancreatic Magnetic Resonance Imaging after Staging Computed Tomography to Evaluate Patients with Pancreatic Ductal Adenocarcinoma
Hye Jin Kim, Mi-Suk Park, Jin Yong Lee, Kyunghwa Han, Yong Eun Chung, Jin-Young Choi, Myeong-Jin Kim, Chang Moo Kang
Cancer Res Treat. 2019;51(1):24-33.   Published online February 5, 2018
DOI: https://doi.org/10.4143/crt.2017.404
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The purpose of this study was to investigate the impact of contrast enhanced pancreatic magnetic resonance imaging (MRI) in resectability and prognosis evaluation after staging computed tomography (CT) in patients with pancreatic ductal adenocarcinoma (PDA).
Materials and Methods
From January 2005 to December 2012, 298 patients were diagnosed to have potentially resectable stage PDA on CT. Patients were divided into CT+MR (patients underwent both CT and MRI; n=216) and CT only groups (n=82). Changes in resectability staging in the CT+MR group were evaluated. The overall survival was compared between the two groups. The recurrence-free survival and median time to liver metastasis after curative surgery were compared between the two groups.
Results
Staging was changed from resectable on CT to unresectable state on MRI in 14.4% of (31 of 216 patients) patients of the CT+MR group. The overall survival and recurrence-free survival rates were not significantly different between the two groups (p=0.162 and p=0.721, respectively). The median time to liver metastases after curative surgery in the CT+MR group (9.9 months) was significantly longer than that in the CT group (4.2 months) (p=0.011).
Conclusion
Additional MRI resulted in changes of resectability and treatment modifications in a significant proportion of patients who have potentially resectable state at CT and in prolonged time to liver metastases in patients after curative surgery. Additional MRI to standard staging CT can be recommended for surgical candidates of PDA.

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The Association of Acquired T790M Mutation with Clinical Characteristics after Resistance to First-Line Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor in Lung Adenocarcinoma
Yen-Hsiang Huang, Kuo-Hsuan Hsu, Jeng-Sen Tseng, Kun-Chieh Chen, Chia-Hung Hsu, Kang-Yi Su, Jeremy J. W. Chen, Huei-Wen Chen, Sung-Liang Yu, Tsung-Ying Yang, Gee-Chen Chang
Cancer Res Treat. 2018;50(4):1294-1303.   Published online January 4, 2018
DOI: https://doi.org/10.4143/crt.2017.512
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The main objective of this study was to investigate the relationship among the clinical characteristics and the frequency of T790M mutation in advanced epidermal growth factor receptor (EGFR)‒mutant lung adenocarcinoma patients with acquired resistance after firstline EGFR‒tyrosine kinase inhibitor (TKI) treatment.
Materials and Methods
We enrolled EGFR-mutant stage IIIB-IV lung adenocarcinoma patients, who had progressed to prior EGFR-TKI therapy, and evaluated their rebiopsy EGFR mutation status.
Results
A total of 205 patients were enrolled for analysis. The overall T790M mutation rate of rebiopsy was 46.3%. The T790M mutation rates among patients with exon 19 deletion mutation, exon 21 L858R point mutation, and other mutations were 55.0%, 37.3%, and 27.3%, respectively. Baseline exon 19 deletion was associated with a significantly higher frequency of T790M mutation (adjusted odds ratio, 2.14; 95% confidence interval [CI], 1.20 to 3.83; p=0.010). In the exon 19 deletion subgroup, there was a greater prevalence of T790M mutation than other exon 19 deletion subtypes in patients with the Del E746-A750 mutation (61.6% vs. 40.6%; odds ratio, 2.35; 95% CI, 1.01 to 5.49; p=0.049). The progression-free survival (PFS) of first-line TKI treatment > 11 months was also associated with a higher T790M mutation rate (54.1% vs. 39.3%; adjusted odds ratio, 1.82; 95% CI, 1.02 to 3.25; p=0.044). Patients who underwent rebiopsy at metastatic sites had more chance to harbor T790M mutation (52.6% vs. 33.8%; adjusted odds ratio, 1.97; 95% CI, 1.06 to 3.67; p=0.032).
Conclusion
PFS of first-line EGFR-TKI, rebiopsy site, EGFR exon 19 deletion and its subtype Del E746- A750 mutation are associated with the frequency of T790M mutation.

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    Cancer Biology & Therapy.2020; 21(8): 741.     CrossRef
  • Post-Progression Survival in Secondary EGFR T790M-Mutated Non-Small-Cell Lung Cancer Patients With and Without Osimertinib After Failure of a Previous EGFR TKI
    Chi-Lu Chiang, Hsu-Ching Huang, Chia-I Shen, Yung-Hung Luo, Yuh-Min Chen, Chao-Hua Chiu
    Targeted Oncology.2020; 15(4): 503.     CrossRef
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  • Prior EGFR-TKI Treatment in EGFR-Mutated NSCLC Affects the Allele Frequency Fraction of Acquired T790M and the Subsequent Efficacy of Osimertinib
    Chih-Hsi Scott Kuo, Chi-Hsien Huang, Chien-Ying Liu, Stelios Pavlidis, Ho-Wen Ko, Fu-Tsai Chung, Tin-Yu Lin, Chih-Liang Wang, Yi-Ke Guo, Cheng-Ta Yang
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  • Frecuencia de mutación T790M determinada por biopsia líquida en pacientes con cáncer pulmonar de células no pequeñas después de la progresión a inhibidores de tirosina cinasa contra EGFR en primera línea
    Jorge Arturo Alatorre-Alexander, Patricio Santillán-Doherty, María del Rosario Flores-Soto, Luis Manuel Martínez-Barrera, Jerónimo Rafael Rodríguez-Cid, Carla Paola Sánchez-Ríos
    NCT Neumología y Cirugía de Tórax.2019; 78(4): 348.     CrossRef
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Intercalated Treatment Following Rebiopsy Is Associated with a Shorter Progression-Free Survival of Osimertinib Treatment
Jeng-Sen Tseng, Tsung-Ying Yang, Kun-Chieh Chen, Kuo-Hsuan Hsu, Yen-Hsiang Huang, Kang-Yi Su, Sung-Liang Yu, Gee-Chen Chang
Cancer Res Treat. 2018;50(4):1164-1174.   Published online December 11, 2017
DOI: https://doi.org/10.4143/crt.2017.460
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Epidermal growth factor receptor (EGFR) T790M mutation serves as an important predictor of osimertinib efficacy. However, little is known about how it works among patients with various timings of T790M emergence and treatment.
Materials and Methods
Advanced EGFR-mutant lung adenocarcinoma patients with positive T790M mutation in tumor were retrospectively enrolled and observed to determine the outcomes of osimertinib treatment. We evaluated the association between patients’ characteristics and the efficacy of osimertinib treatment, particularly with respect to the timing of T790M emergence and osimertinib prescription.
Results
A total of 91 patients were enrolled, including 14 (15.4%) with primary and 77 (84.6%) with acquired T790M mutation. The objective response rate and disease controlratewere 60.9% and 85.1%, respectively. The median progression-free survival (PFS) and overall survival were 11.5 months (95% confidence interval [CI], 9.0 to 14.0) and 30.4 months (95% CI, 11.3 to 49.5), respectively. There was no significant difference in response rate and PFS between primary and acquired T790M populations. In the acquired T790M subgroup, patientswho received osimertinib after T790M had been confirmed by rebiopsy had a longer PFS than those with intercalated treatments between rebiopsy and osimertinib prescription (14.0 months [95% CI, 9.0 to 18.9] vs. 7.2 months [95% CI, 3.7 to 10.8]; adjusted hazard ratio, 0.48 [95% CI, 0.24 to 0.98; p=0.043]). Rebiopsy timing did not influence the outcome.
Conclusion
Osimertinib prescription with intercalated treatment following rebiopsy but not the timing of T790M emergence influenced the treatment outcome. We suggest that it is better to start osimertinib treatment once T790M mutation has been confirmed by biopsy.

Citations

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    Targeted Oncology.2020; 15(4): 503.     CrossRef
  • Prior EGFR-TKI Treatment in EGFR-Mutated NSCLC Affects the Allele Frequency Fraction of Acquired T790M and the Subsequent Efficacy of Osimertinib
    Chih-Hsi Scott Kuo, Chi-Hsien Huang, Chien-Ying Liu, Stelios Pavlidis, Ho-Wen Ko, Fu-Tsai Chung, Tin-Yu Lin, Chih-Liang Wang, Yi-Ke Guo, Cheng-Ta Yang
    Targeted Oncology.2019; 14(4): 433.     CrossRef
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EGFR Mutation Status in Lung Adenocarcinoma-Associated Malignant Pleural Effusion and Efficacy of EGFR Tyrosine Kinase Inhibitors
Jiyoul Yang, Ok-Jun Lee, Seung-Myoung Son, Chang Gok Woo, Yusook Jeong, Yaewon Yang, Jihyun Kwon, Ki Hyeong Lee, Hye Sook Han
Cancer Res Treat. 2018;50(3):908-916.   Published online September 19, 2017
DOI: https://doi.org/10.4143/crt.2017.378
AbstractAbstract PDFPubReaderePub
Purpose
Malignant pleural effusions (MPEs) are often observed in lung cancer, particularly adenocarcinoma. The aim of this study was to investigate epidermal growth factor receptor (EGFR) mutation status in lung adenocarcinoma-associated MPEs (LA-MPEs) and its correlation with efficacy of EGFR tyrosine kinase inhibitor (TKI) therapy.
Materials and Methods
Samples comprised 40 cell blocks of pathologically-confirmed LA-MPEs collected before the start of EGFR TKI therapy. EGFR mutation status was re-evaluated by peptide nucleic acid clamping and the clinical outcomes of EGFR TKI‒treated patients were analyzed retrospectively.
Results
EGFR mutations were detected in 72.5% of LA-MPE cell blocks (29/40). The median progression-free survival for patients with EGFR mutations in LA-MPEs was better than that for patients with wild-type EGFR (7.33 months vs. 2.07 months; hazard ratio, 0.486; 95% confidence interval, 0.206 to 1.144; p=0.032). The objective response rate (ORR) of 26 patients with EGFR mutations in LA-MPEs among the 36 patients with measurable lesions was 80.8%, while the ORR of the 10 patients with wild-type EGFR in LA-MPEs was 10% (p < 0.001). Among the 26 patients with EGFR mutations in LA-MPEs, the ORR of target lesions and LA-MPEs were 88.5% and 61.5%, respectively (p=0.026).
Conclusion
EGFR mutation status in cell blocks of LA-MPEs confirmed by pathologic diagnosis is highly predictive of EGFR TKI efficacy. For patients with EGFR mutations in LA-MPEs, the response to EGFR TKIs seems to be worse for pleural effusions than for solid tumors.

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The Role of Consolidation Chemoradiotherapy in Locally Advanced Pancreatic Cancer Receiving Chemotherapy: An Updated Systematic Review and Meta-Analysis
Jeffrey S. Chang, Yen-Feng Chiu, Jih-Chang Yu, Li-Tzong Chen, Hui-Ju Ch’ang
Cancer Res Treat. 2018;50(2):562-574.   Published online June 9, 2017
DOI: https://doi.org/10.4143/crt.2017.105
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The role of consolidation chemoradiation (CCRT) after systemic chemotherapy in locally advanced pancreatic cancer (LAPC) is still controversial. We aim to evaluate the effectiveness of CCRT in LAPC using systematic review and meta-analysis of prospective studies.
Materials and Methods
Prospective clinical trials of LAPC receiving chemotherapy with or without subsequent CCRT were included in the analysis. We systematically searched in PubMed, MEDLINE, Embase, and Web of Science. The primary outcome of interest was 1-year survival. Secondary endpoints were median overall survival, progression-free survival, toxicity, and resection rate.
Results
Forty-one studies with 49 study arms were included with a total of 1,018 patients receiving CCRT after induction chemotherapy (ICT) and 954 patients receiving chemotherapy alone. CCRT after ICT did not improve 1-year survival significantly in LAPC patients compared with chemotherapy alone (58% vs. 52%). ICT lasted for at least 3 months revealed significantly improved survival of additional CCRT to LAPC patients compared to chemotherapy alone (65% vs. 52%). A marginal survival benefit of consolidation CCRT was noted in studies using maintenance chemotherapy (59% vs. 52%), and fluorouracil-based CCRT (64% vs. 52%), as well as in studies conducted after the 2010 (64% vs. 55%).
Conclusion
The survival benefit of ICT+CCRT over chemotherapy alone in treating LAPC was noted when ICT lasted for at least 3 months. Fluorouracil-based CCRT, and maintenance chemotherapy were associated with improved clinical outcomes.

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Effect of Adjuvant Chemotherapy after Complete Resection for Pathologic Stage IB Lung Adenocarcinoma in High-Risk Patients as Defined by a New Recurrence Risk Scoring Model
Hyo Joon Jang, Sukki Cho, Kwhanmien Kim, Sanghoon Jheon, Hee Chul Yang, Dong Kwan Kim
Cancer Res Treat. 2017;49(4):898-905.   Published online January 18, 2017
DOI: https://doi.org/10.4143/crt.2016.312
AbstractAbstract PDFPubReaderePub
Purpose
We conducted a retrospective analysis to determine if adjuvant chemotherapy prolongs overall survival in patients with pathologic stage IB lung adenocarcinoma who had undergone complete resection and were defined as high-risk by a newly developed recurrence risk scoring model.
Materials and Methods
Patientswho underwent curative resection for stage IB lung adenocarcinomawere analyzed with a newly developed recurrence risk scoring model and divided into a low-risk group and a high-risk group. The patients in the high-risk group were retrospectively divided into two groups based on whether they underwent adjuvant chemotherapy or observation. Recurrence-free survival and overall survival were compared between these two groups.
Results
A total of 328 patients who underwent curative resection between 2000 and 2009 were included in this study, of whom 110 (34%) received adjuvant chemotherapy and 218 (67%) underwent observation without additional treatment. According to our risk model, 167 patients (51%) were high-risk and 161 (49%) were low-risk. The 5-year recurrence-free survival rates and overall survival were 84.4% and 91.5% in low-risk patients and 53.9% and 74.7% in high-risk patients (p < 0.001). In high-risk patients, the 5-year overall survival rates were 77% among patients who underwent observation and 87% among those who underwent adjuvant chemotherapy (p=0.019).
Conclusion
Adjuvant chemotherapy prolonged overall survival among high-risk patients who had undergone complete resection for stage IB lung adenocarcinoma.

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Lung Cancer Epidemiology in Korea
Aesun Shin, Chang-Mo Oh, Byung-Woo Kim, Hyeongtaek Woo, Young-Joo Won, Jin-Soo Lee
Cancer Res Treat. 2017;49(3):616-626.   Published online September 23, 2016
DOI: https://doi.org/10.4143/crt.2016.178
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The current study was undertaken to examine the trends in the lung cancer incidence, mortality, and survival after a diagnosis in Korea.
Materials and Methods
Lung cancer incidence data according to the histologic type and mortality data were obtained from the Korea Central Cancer Registry and the Statistics Korea, respectively. The age-standardized incidence and mortality rates were calculated, and the Joinpoint model and age-period-cohort analyses were used to describe the trends in the rates. The 5-year relative survival rates of lung cancer were also calculated.
Results
Although the number of new lung cancer cases increased between 1999 and 2012, the age-standardized incidence rate decreased by 0.9% per year in men, whereas the incidence in women increased by 1.7% per year over the same time. Until 2010, the most common histologic type in men was squamous cell carcinoma, then adenocarcinoma prevailed thereafter. Since 1999, the most frequent histological type in women was adenocarcinoma. The lung cancer mortality started to decrease in 2002, with a more apparent decline for the younger age groups in both men and women. Overall, the 5-year relative survival rates have improved significantly from 11.2% for men and 14.7% for women among patients diagnosed between 1993 and 1997 to 19.3% for men and 28.2% for women among patients diagnosed between 2008 and 2012, respectively. An improvement in survival rate was observed for all major histology groups.
Conclusion
The epidemiology of lung cancer in Korea has changed over a short time span, with decreasing mortality and improving survival rates. Further study is warranted to determine the cause of these changes.

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Clinicopathological Features of Low-Grade Thyroid-like Nasopharyngeal Papillary Adenocarcinoma
Minhua Li, Jiangguo Wei, Xiaofei Yao, Cheng Wang
Cancer Res Treat. 2017;49(1):213-218.   Published online July 4, 2016
DOI: https://doi.org/10.4143/crt.2016.195
AbstractAbstract PDFPubReaderePub
Purpose
Primary low-grade thyroid-like papillary adenocarcinomas are extremely rare neoplasms that generally originate in the nasopharynx. Here, we describe a novel case of a 15-year-old Chinese girl who was diagnosed with low-grade thyroid-like papillary adenocarcinoma, including a brief review of the literature to reveal the clinicopathological features of low-grade thyroid-like nasopharyngeal papillary adenocarcinoma.
Materials and Methods
Immunohistochemistry was used to evaluate the expression of pan-cytokeratin (CKpan), cytokeratin (CK) 7, thyroid transcription factor 1 (TTF-1), vimentin, epithelial membrane antigen (EMA), thyroglobulin, CD15, S100, P40, CK20, CDX-2, glial fibrillary acidic protein (GFAP), and Ki-67. Additionally, in situ hybridization investigation was utilized to identify the presence of small Epstein-Barr virus (EBV)–encoded RNA.
Results
Histopathological analysis revealed florid proliferation of papillary structures lined by columnar epithelial cells with fibrovascular cores. Immunohistochemically, the neoplastic cells were positive for CKpan, CK7, TTF-1, vimentin, and EMA, but negative for thyroglobulin, CD15, S100, P40, CK20, CDX-2, and GFAP. The Ki-67–labeling index reached 5% in the most concentrated spot. In situ hybridization for EBV was negative.
Conclusion
Due to the distinct rarity of low-grade thyroid-like papillary adenocarcinomaswith a favorable clinical outcome, a nationwide effort to raise public awareness of this neoplasm is required.

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Venous Invasion in Colorectal Cancer: Impact of Morphologic Findings on Detection Rate
Chungsu Hwang, Sojeong Lee, Ahrong Kim, Young-Geum Kim, Sang-Jeong Ahn, Do Youn Park
Cancer Res Treat. 2016;48(4):1222-1228.   Published online February 12, 2016
DOI: https://doi.org/10.4143/crt.2015.429
AbstractAbstract PDFPubReaderePub
Purpose
Venous invasion (VI) is widely accepted as a poor prognostic factor in colorectal cancer (CRC), and is indicated as a high-risk factor determining the use of adjuvant chemotherapy in CRC. However, there is marked interobserver and intraobserver variability in VI identification and marked variability in the real prevalence of VI in CRC.
Materials and Methods
We investigated the detection rate of VI in 93 consecutive cases of T3 or T4 CRC based on the following: original pathology report, review of hematoxylin and eosin (H&E) slides with attention to the “protruding tongue” and “orphan arteriole” signs, and elastic stain as the gold standard.
Results
Overall, the detection rate of VI was significantly increased as follows: 14/93 (15.1%) in the original pathology report, 38/93 (40.9%) in review of H&E slides with attention to the “protruding tongue” and “orphan arteriole” signs, and 45/93 (48.4%) using elastic stain. VI detection based on morphologic features showed 77.8% sensitivity and 91.1% specificity and showed a linear correlation (Spearman correlation coefficient, 0.727; p < 0.001) with VI detected by elastic stain. In addition, improved agreement between detection methods (detection on the basis of morphologic features, κ=0.719 vs. original pathology report, κ=0.318) was observed using kappa statistics.
Conclusion
Slide review with special attention to the “protruding tongue” and “orphan arteriole” signs could be used for better identification of VI in CRC in routine surgical practice.

Citations

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  • Colorectal adenosquamous carcinoma: clinicopathologic analysis of two large cohorts and literature review confirm poor prognosis and reveal prognostic aspects
    Raul S Gonzalez, Rachel K Horton, Xuchen Zhang, Rondell P Graham, Teri A Longacre, Anupamjit Mehrotra, Daniela S Allende, Kelsey E McHugh, Jinru Shia, Maria Westerhoff, Amitabh Srivastava, Wei Chen, Jennifer Vazzano, Paul E Swanson, Deyali Chatterjee, Has
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  • Routine elastin staining improves venous invasion detection in colorectal carcinoma
    Hisham F. Bahmad, Ferial Alloush, Ali Salami, Rachel Sawah, Ciara Lusnia, Ekim Kilinc, Tyson Sutherland, Sarah Alghamdi, Robert J. Poppiti
    Annals of Diagnostic Pathology.2023; 66: 152170.     CrossRef
  • The Usefulness of Elastin Staining to Detect Vascular Invasion in Cancer
    Jeffrey Gonzalez, Hisham F. Bahmad, Stephanie Ocejo, Alvaro Abreu, Meagan Popp, Samantha Gogola, Vielka Fernandez, Monica Recine, Robert Poppiti
    International Journal of Molecular Sciences.2023; 24(20): 15264.     CrossRef
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Systemic Inflammatory Response Markers and CA-125 Levels in Ovarian Clear Cell Carcinoma: A Two Center Cohort Study
Hee Seung Kim, Hwa-Young Choi, Maria Lee, Dong Hoon Suh, Kidong Kim, Jae Hong No, Hyun Hoon Chung, Yong Beom Kim, Yong Sang Song
Cancer Res Treat. 2016;48(1):250-258.   Published online March 6, 2015
DOI: https://doi.org/10.4143/crt.2014.324
AbstractAbstract PDFPubReaderePub
Purpose
We compared the predictive and prognostic values of leukocyte differential counts, systemic inflammatory (SIR) markers and cancer antigen 125 (CA-125) levels, and identified the most useful marker in patients with ovarian clear cell carcinoma (OCCC).
Materials and Methods
The study included 109 patients with OCCC who did not have any inflammatory conditions except endometriosis, and underwent primary debulking surgery between 1997 and 2012. Leukocyte differential counts (neutrophil, lymphocyte, monocyte, eosinophil, basophil, and platelet), SIR markers including neutrophil to lymphocyte ratio (NLR), monocyte to lymphocyte ratio (MLR), and platelet to lymphocyte ratio (PLR), and CA-125 levels were estimated to select potential markers for clinical outcomes.
Results
Among potential markers (neutrophil, monocyte, platelet, NLR, MLR, PLR, and CA-125 levels) selected by stepwise comparison, CA-125 levels were best at predicting advanced stage disease, suboptimal debulking and platinum-resistance (cut-off values, ≥ 46.5, ≥ 11.45, and ≥ 66.4 U/mL; accuracies, 69.4%, 78.7%, and 68.5%) while PLR ≥ 205.4 predicted noncomplete response (CR; accuracy, 71.6%) most accurately. Moreover, PLR < 205.4 was an independent factor for the reduced risk of non-CR (adjusted odds ratio, 0.17; 95% confidence interval [CI], 0.04 to 0.69), and NLR < 2.8 was a favorable factor for improved progression-free survival (PFS; adjusted hazard ratio, 0.49; 95% CI, 0.25 to 0.99) despite lack of a marker for overall survival among the potential markers.
Conclusion
CA-125 levels may be the most useful marker for predicting advanced-stage disease. Suboptimal debulking and platinum-resistance, and PLR and NLR may be most effective to predict non-CR and PFS in patients with OCCC.

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Case Report
A Case Report of Partial Nephrectomy of Mucinous Cystadenocarcinoma in Kidney and Its Literature Review
Sung Han Kim, Heong Dong Yuk, Weon Seo Park, Sun Ho Kim, Jae Young Joung, Ho Kyung Seo, Kang Hyun Lee, Jinsoo Chung
Cancer Res Treat. 2016;48(2):838-842.   Published online February 13, 2015
DOI: https://doi.org/10.4143/crt.2014.219
AbstractAbstract PDFPubReaderePub
Mucinous cystadenocarcinoma (MC) of the kidney is a rare epithelial tumor originating from the renal pelvic urothelium and few study cases have been reported. Because of the rarity of these tumors and their unknown histogenesis, its diagnosis is difficult until surgical exploration. We report here on a 55-year-old man referred to the urology department from the hepatology department because of a cystic renal mass measuring approximately 5 cm in size, which was detected incidentally under ultrasonography during the routine examination of liver. The renal mass was finally diagnosed as MC originating from kidney after partial nephrectomy and the patient still showed no evidence of recurrence until 12 months postoperatively. This is the first report on a case of renal MC in a patient who underwent partial nephrectomy. The aim of this report is to present our unusual case of MC and also review the previous literature on the pathological and radiological aspects of MC of kidney.

Citations

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  • Mucinous adenocarcinoma in kidneys with developmental anomalies - a report of two cases
    Kasi Viswanath Gali, Arun Chawla, K. R. Surag, Sunil Pillai Bhaskara, Padmaraj Hegde
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Original Articles
Identification of EGFR Mutations by Immunohistochemistry with EGFR Mutation–Specific Antibodies in Biopsy and Resection Specimens from Pulmonary Adenocarcinoma
Chi Hong Kim, Seung Hoon Kim, Sonya Youngju Park, Jinyoung Yoo, Sung Kyoung Kim, Hoon Kyo Kim
Cancer Res Treat. 2015;47(4):653-660.   Published online January 30, 2015
DOI: https://doi.org/10.4143/crt.2014.118
AbstractAbstract PDFPubReaderePub
Purpose
Mutation-specific antibodies have recently been developed for identification of epidermal growth factor receptor (EGFR) mutations by immunohistochemistry (IHC). This study was designed to investigate whether the type of specimen (biopsy vs. resection) would make a difference in determining mutation status by IHC, and to evaluate whether biopsies are suitable for detection of mutant EGFR protein.
Materials and Methods
IHC was performed using mutation-specific antibodies for E746-A750 deletion (DEL) and L858R point mutation (L858R) in biopsies and tissue microarrays of resected tumors from 154 patients with pulmonary adenocarcinoma. Results were then compared with DNA sequencing data.
Results
Molecular-based assays detected EGFR mutations in 62 patients (40.3%), including 14 (9.1%) with DEL, and 31 (20.1%) with L858R. IHC with two mutation-specific antibodies showed a homogeneous staining pattern, and correctly identified EGFRmutation status in 89% (137/154). Overall (biopsy/resection) sensitivity, specificity, positive predictive value, and negative predictive value were 75.6% (78.3%/72.7%), 94.5% (90.9%/96.3%), 85% (78.3%/88.9%), and 90.4% (90.9%/89.7%), respectively.
Conclusion
Our data showed that IHC using EGFR mutation–specific antibodies is useful for detection of EGFRmutations with high specificity and good sensitivity not only for resection specimens but also for biopsy materials. Therefore, IHC using EGFRmutation–specific antibodies may preclude a second biopsy procedure to obtain additional tissues for identification of EGFR mutations by molecular assays in biopsies from advanced cancer, particularly when tumor cells in the samples are limited.

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Safety of Fertility-Sparing Surgery in Primary Mucinous Carcinoma of the Ovary
Jung-Yun Lee, Yu Ri Jo, Tae Hun Kim, Hee Seung Kim, Min A Kim, Jae Weon Kim, Noh Hyun Park, Yong-Sang Song
Cancer Res Treat. 2015;47(2):290-305.   Published online August 29, 2014
DOI: https://doi.org/10.4143/crt.2014.004
AbstractAbstract PDFPubReaderePub
Purpose
The aim of this study is to evaluate the safety of fertility-sparing surgery as the treatment for patients with primary mucinous epithelial ovarian cancer.
Materials and Methods
A retrospective study of patients with mucinous ovarian cancer between 1991 and 2010 was performed. The demographics and survival outcomes were compared between patients who underwent fertility-sparing surgery and those who underwent radical surgery.
Results
A total of 110 patients underwent primary surgery. At the time of surgery, tumors appeared to be grossly confined to the ovaries in 90 patients, and evidence of metastasis was definite in 20 patients. Of the 90 patients with tumors that appeared to be grossly confined to the ovaries at surgical exploration, 35 (38.9%) underwent fertility-sparing surgery. The Kaplan- Meier curve and the log rank test showed no difference in either recurrence-free survival (p=0.792) or disease-specific survival (p=0.706) between the two groups. Furthermore, there was no significant difference in recurrence-free survival (p=0.126) or disease-specific survival (p=0.377) between the two groups, even when the analysis was limited to women below the age of 40. In a multivariate Cox model, fertility-sparing surgery had no effect on either recurrence-free survival (recurrence hazard ratio [HR], 1.20; 95% confidence interval [CI], 0.25 to 5.71) or disease-specific survival (death HR, 0.88; 95% CI, 0.17 to 4.60).
Conclusion
Fertility-sparing surgery in primary mucinous cancer grossly confined to the ovaries may be a safe option and one not associated with an increase in recurrence or mortality.

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Diagnostic Value of Circulating Extracellular miR-134, miR-185, and miR-22 Levels in Lung Adenocarcinoma-Associated Malignant Pleural Effusion
Yoon Mi Shin, Jieun Yun, Ok-Jun Lee, Hye-Suk Han, Sung-Nam Lim, Jin Young An, Ki Hyeong Lee, Ki Man Lee, Kang Hyeon Choe
Cancer Res Treat. 2014;46(2):178-185.   Published online April 15, 2014
DOI: https://doi.org/10.4143/crt.2014.46.2.178
AbstractAbstract PDFPubReaderePub
Purpose

The accurate and timely diagnosis of malignant pleural effusion (MPE) in lung cancer patients is important because MPE has a poor prognosis and is classified as stage IV disease. Molecular biomarkers for pleural effusion, such as circulating extracellular microRNAs (miRNAs) isolated from pleural fluid, may help in the diagnosis of MPE. The present study examined whether miRNAs that are deregulated in lung cancer (miR-134, miR-185, and miR-22) can serve as diagnostic markers for lung adenocarcinoma-associated MPE (LA-MPE).

Materials and Methods

Real-time reverse transcription quantitative polymerase chain reaction was used to measure the expression of the three miRNAs in samples from 87 patients with pleural effusion comprising 45 LA-MPEs and 42 benign pleural effusions (BPEs). The area under the receiver operating characteristic curve (AUC) was then used to evaluate the diagnostic performance of each of the three miRNAs and compare it with that of the common tumor marker, carcinoembryonic antigen (CEA).

Results

The expression of all three miRNAs was significantly lower in LA-MPE than in BPE (p <0.001). The AUCs for miR-134, miR-185, miR-22, and CEA were 0.721, 0.882, 0.832, and 0.898, respectively. Combining CEA with the three miRNAs increased the diagnostic performance, yielding an AUC of 0.942 (95% confidence interval, 0.864 to 0.982), with a sensitivity of 91.9% and a specificity of 92.5%.

Conclusion

The present study suggests that the expression levels of circulating extracellular miR-134, miR-185, and miR-22 in patients with pleural effusion may have diagnostic value when differentiating between LA-MPE and BPE.

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