Cancer Research and Treatment

Review Article

Diagnostic Challenges and Clinical Implications of Microsatellite Instability/Mismatch Repair Deficiency in Solid Tumors: Yoonjin Kwak, Jeong Mo Bae, Hye Seung Lee; Cancer Res Treat. 2026;58(1):1-14. Published online December 26, 2025; DOI: https://doi.org/10.4143/crt.2025.1161

The mismatch repair (MMR) system plays a crucial role in correcting replication errors; when the MMR system is deficient (dMMR), replication errors (particularly within microsatellites) accumulate throughout the genome, leading to microsatellite instability (MSI). The key MMR genes include MLH1, MSH2, MSH6, and PMS2. Germline mutations in these genes are associated with Lynch syndrome, whereas in sporadic solid tumors, dMMR is often caused by hypermethylation of the MLH1 promoter. As the clinical use of dMMR/MSI expands, the importance of reliable testing for dMMR or MSI in companion diagnostics continues to increase. dMMR/MSI is diagnosed using immunohistochemistry (IHC) for MMR proteins, polymerase chain reaction with fragmentation analysis, or next-generation sequencing. Although IHC has technical limitations, it requires less tissue, has a short processing time, and is cost-effective. Experienced or specialized pathologists and educational efforts are helpful for reliable diagnosis, in addition to the technical aspects. Solid tumors with dMMR/MSI exhibit distinct clinicopathological features, including prognostic significance and a predictive role in adjuvant cytotoxic chemotherapy. Solid tumors with dMMR/MSI are also characterized by a higher tumor mutational burden and abundant immune cell infiltration, making them promising candidates for immune checkpoint inhibitor therapy. However, the oncogenic processes and immune microenvironment are not identical across the organs of origin, between patients, and even within the same patient, which should be considered in future studies. This review provides an overview of the practical aspects of dMMR/MSI testing, along with the molecular mechanisms and immune microenvironments associated with dMMR/MSI solid tumors.

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Evaluation of Droplet Digital PCR Assay for the Detection of Microsatellite Instability in Colorectal, Gastric, and Endometrial Cancers
Yousun Chung, Sujin Oh, Soo Kyung Nam, Hyunji Kim, Cheol Lee, Gyeong Hoon Kang, Hyeon Jeong Oh, Hye Seung Lee, Kyoung Un Park
Diagnostics.2026; 16(10): 1550. CrossRef
New progress and clinical research translation of immune checkpoint inhibitors in systemic therapy of gallbladder cancer
Fuhong Li, Yuxiao Wang, Zhiren Xu, Meng Zhu, Kun Su, Xiawei Yang, Tao Wu
Frontiers in Immunology.2026;[Epub] CrossRef

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Original Articles

Analysis of T-Cell Subsets Using Multiplex Immunohistochemistry and Clinical Outcomes of Immune Checkpoint Inhibitors in Advanced Gastric Cancer Patients: Tae-Yong Kim, Jeesun Yoon, Dae-Won Lee, Yoonjin Kwak, Hye Seung Lee, Do-Youn Oh; Received April 28, 2025 Accepted September 7, 2025 Published online September 9, 2025; DOI: https://doi.org/10.4143/crt.2025.458 [Epub ahead of print]

Abstract PDF Supplementary Material PubReader ePub

Purpose
As immunotherapy has become essential in the treatment of gastric cancer (GC), there has been growing interest in T-cells, which play a key role in immunotherapy. In this study, we evaluated the impact of T-cell subsets on immune responsiveness to immune checkpoint inhibitors (ICIs) in GC using multiplex immunohistochemistry (mIHC).
Materials and Methods
Eighty-four GC patients treated with ICIs were enrolled, and we repeated the staining-scanning-stripping procedure nine times to assess different kinds of T-cells or cell-surface immune checkpoints in a single tissue section.
Results
The proportions of patients with microsatellite instability (MSI)–high, Epstein-Barr virus (EBV), and non-MSI/non-EBV were 8.3%, 3.6%, and 88.1%. A high cytotoxic T-cell (T_cyto) density was related to longer overall survival (OS). GC with a high ratio of T_cyto/total T-cells (T_total) and a low ratio of regulatory T-cells (T_reg)/T_total showed better OS. A high density of programmed death-1 (PD-1)– or TIM-3–expressing T_cyto were also associated with longer OS than a low density of those. Among memory T-cells (T_mem) subsets, GC with a high ratio of memory T_cyto/T_mem and a low ratio of memory T_reg/T_mem showed prolonged OS. Better tumor responses were observed in GC with a high ratio of T_cyto/T_total and memory T_cyto/T_mem.
Conclusion
T-cell subsets within the tumor microenvironment were associated with the clinical efficacy of ICIs in GC. PD-1– or TIM-3–expressing T-cells were also associated with response to ICIs, while T_mem subsets were associated with survival. mIHC is a feasible method for evaluating T-cell subsets in archival gastric tumor tissue.

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T cell-mediated immune function in gastric cancer: a bibliometric overview of the last 20 years (2006-2025)
Tao Wang, Li-Li Li, Chun-Yan Wang, Wen-Jing Sui, Mai-Qing Yang
Frontiers in Oncology.2026;[Epub] CrossRef

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Gastrointestinal cancer

Microbial Dynamics across Molecular Subtypes and Prognostic Significance of Lactobacillus in Gastric Cancer: Soo Kyung Nam, Juhyeong Park, Sujin Oh, Yoonjin Kwak, Cheol Min Shin, Kyoung Un Park, Nak-Jung Kwon, Seong-Ho Kong, Do Joong Park, Hyuk-Joon Lee, Han-Kwang Yang, Hye Seung Lee; Cancer Res Treat. 2026;58(3):824-845. Published online July 17, 2025; DOI: https://doi.org/10.4143/crt.2025.449

Abstract PDF Supplementary Material PubReader ePub: Purpose
Recent studies have revealed a diverse gastric microbiota beyond Helicobacter pylori, suggesting a role in gastric cancer (GC). We aimed to investigate the composition and characteristics of the microbiota in GC and non-cancerous gastric mucosa (NC), with a particular focus on their relationship to molecular subtypes.
Materials and Methods
We conducted 16S rRNA sequencing and whole transcriptomic analysis on fresh-frozen GC and NC tissue samples from 192 GC patients, as well as saliva samples from 12 GC patients and 18 healthy individuals. Microsatellite instability (MSI), Epstein-Barr virus (EBV) in situ hybridization, and immunohistochemistry for p53 and E-cadherin were used to define molecular subtypes.
Results
GC tissues exhibited significantly higher diversity compared to matched NC tissues, with microbial profiles marked by decreased Helicobacter and increased Streptococcus, Prevotella, and Lactobacillus. Saliva samples predominantly contained oral bacteria and exhibited distinct microbial profiles from gastric tissues. In GC tissue, Helicobacter abundance was negatively correlated with key immune checkpoint genes (CTLA-4, PDCD1, CD274, and LAG3), whereas Prevotella, Streptococcus, and Fusobacterium were positively correlated. MSI-high and EBV-positive subtypes showed lower levels of Helicobacter but higher levels of Lactobacillus, Prevotella, and Streptococcus compared to the epithelial-mesenchymal transition–like subtype. Notably, within MSI-high GC, a subgroup characterized by Lactobacillus-enriched and otherwise microbiota-depleted profiles was significantly associated with poorer overall and disease-free survival.
Conclusion
These findings underscore distinct microbial patterns across GC molecular subtypes, suggesting potential biomarkers for GC diagnosis and treatment.

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Case Report

ALK Inhibition in a Patient with Inflammatory Myofibroblastic Tumor Harboring CARS1-ALK Fusion: Songji Choi, Miso Kim, Sheehyun Kim, Taekeun Park, Yoonjin Kwak, Jeong Mo Bae, Hongseok Yun, Jee Hyun Kim; Cancer Res Treat. 2025;57(3):899-904. Published online December 18, 2024; DOI: https://doi.org/10.4143/crt.2024.1184

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Inflammatory myofibroblastic tumor (IMT) is a rare entity, primarily affecting young individuals, often involving the abdomen, pelvis, or lung. Approximately 50% of IMTs harbor anaplastic lymphoma kinase (ALK) gene rearrangements, making ALK inhibitors a viable treatment. We report a case of a 40-year-old female with metastatic IMT harboring a CARS1-ALK fusion. Initial chemotherapy failed, but targeted therapy with alectinib through the KOrean Precision Medicine Networking Group Study of MOlecular profiling guided therapy based on genomic alterations in advanced Solid tumors (KOSMOS)-II study led to significant tumor regression and ongoing, durable clinical improvement of 19 months. This case highlights the importance of precision medicine and raises the reappraisal of targeted agents outside of approved indications for rare cancers with actionable genomic alterations.

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Artificial Intelligence in Lung Cancer: A Narrative Review of Recent Advances in Diagnosis, Biomarker Discovery, and Drug Development
Srikanth Basety, Renuka Gudepu, Aditya Velidandi
Pharmaceutics.2026; 18(2): 201. CrossRef
Gastric inflammatory myofibroblastic tumor in adults: a case report and literature review
Zhenxuan Chen, Kebing Chen, Yuting Gu, Tao Peng
Frontiers in Oncology.2026;[Epub] CrossRef
Inflammatory myofibroblastic tumors of the colon in pediatrics: clinical presentation, management, and outcomes—A case report and systematic review of literature
Ismael Elhalaby, Omar Koura, Rofyda Elhalaby, Wael Zeina, Mohamed Shareef, Essam Elhalaby
International Journal of Colorectal Disease.2025;[Epub] CrossRef
Carboplatin/etoposide/ifosfamide

Reactions Weekly.2025; 2075(1): 90. CrossRef

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Original Articles

Gastrointestinal cancer

Effector Function Characteristics of Exhausted CD8+ T-Cell in Microsatellite Stable and Unstable Gastric Cancer: Dong-Seok Han, Yoonjin Kwak, Seungho Lee, Soo Kyung Nam, Seong-Ho Kong, Do Joong Park, Hyuk-Joon Lee, Nak-Jung Kwon, Hye Seung Lee, Han-Kwang Yang; Cancer Res Treat. 2024;56(4):1146-1163. Published online April 12, 2024; DOI: https://doi.org/10.4143/crt.2024.317

Abstract PDF PubReader ePub

Purpose
Gastric cancer exhibits molecular heterogeneity, with the microsatellite instability–high (MSI-H) subtype drawing attention for its distinct features. Despite a higher survival rate, MSI-H gastric cancer lack significant benefits from conventional chemotherapy. The immune checkpoint inhibitors, presents a potential avenue, but a deeper understanding of the tumor immune microenvironment of MSI-H gastric cancer is essential.
Materials and Methods
We explored the molecular characteristics of CD8+ T-cell subtypes in three MSI-H and three microsatellite stable (MSS) gastric cancer samples using single-cell RNA sequencing and spatial transcriptome analysis.
Results
In MSI-H gastric cancer, significantly higher proportions of effector memory T cell (Tem), exhausted T cell (Tex), proliferative exhausted T cell (pTex), and proliferative T cell were observed, while MSS gastric cancer exhibited significantly higher proportions of mucosal-associated invariant T cell and natural killer T cell. In MSI-H gastric cancer, Tex and pTex exhibited a significant upregulation of the exhaustion marker LAG3, as well as elevated expression of effector function markers such as IFNG, GZMB, GZMH, and GZMK, compared to those in MSS gastric cancer. The interferon γ (IFN-γ) signaling pathway of Tex and pTex was retained compared to those of MSS gastric cancer. The spatial transcriptome analysis demonstrates the IFN-γ signaling pathway between neighboring Tex and malignant cell, showcasing a significantly elevated interaction in MSI-H gastric cancer.
Conclusion
Our study reveals novel finding indicating that IFN-γ signaling pathway is retained in Tex and pTex of MSI-H gastric cancer, offering a comprehensive perspective for future investigations into immunotherapy for gastric cancer.

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Gallic acid potentiates the tumour-killing function of CD8+ T cells in gastric cancer
Si Chen, HaiBin Wang, Meixu Lei, Yumin Li, Qi Wang, Hengxin Wang, Yifei Shen, Xuejie Su, Yali Zhou
Journal of Pharmacy and Pharmacology.2026;[Epub] CrossRef
Exploring the molecular pathology and tumor microenvironment in gastric cancer liver metastasis
Jialu Zhuang, Chao Hu, Lei Lei, Yimeng Sang, Qi Sun, Hongping Xia
Hepatoma Research.2026;[Epub] CrossRef
Advances in Spatial Multi-Omics in Gastric Cancer
Hongfei Yan, Yang Liu
Cells.2026; 15(6): 535. CrossRef
Immunotherapy rechallenge in gastric cancer: resistance mechanisms, molecular stratification, and precision decision-making
Yu-cai Jiang, Lin-lin Zheng, Ming-gui Fu, Bi-jin Zheng
Frontiers in Immunology.2026;[Epub] CrossRef
Precision oncology in gastric cancer: navigating molecular subtypes, therapeutic targets, and future horizons
Yanyun Hong, Xiaodong Wang, Hang Yu, Xiaosun Liu, Chao Tang
Cellular Oncology.2026;[Epub] CrossRef
New Functions of Mitochondrial Dysfunction in Gastric Cancer: From Molecular Processes to Potential Treatments
Huanhuan Liu, Yating Zhang, Juan Wang, Min Qiao, Qinghong Guo
International Journal of Molecular Sciences.2026; 27(14): 6305. CrossRef
Neurogranin facilitates maintaining the immunosuppressive state of hepatocellular carcinoma by promoting TGF-β1 secretion
Dongjie Ye, Zhu Zhang, Yuxin Yao, Banglun Pan, Hao Wu, Xinyu Zhang, Xiaoqian Wang, Nanhong Tang
International Journal of Biological Macromolecules.2025; 311: 143716. CrossRef
T-cell senescence: Unlocking the tumor immune “Dark Box” - A multidimensional analysis from mechanism to tumor immunotherapeutic intervention
Jia Cheng, Jian Zheng, Chen Ma, Yongzhang Li, Hua Hao
Seminars in Cancer Biology.2025; 113: 190. CrossRef
Hybrid model for predicting microsatellite instability in colorectal cancer using hematoxylin & eosin-stained images and clinical features
Hangping Wei, Xiaowei Zhang, Zhen Zhou, Jianbin Xie, Weidong Han, Xiaofang Dong
Frontiers in Oncology.2025;[Epub] CrossRef
Simvastatin induces ferroptosis and activates anti-tumor immunity to sensitize anti-PD-1 immunotherapy in microsatellite stable gastric cancer
Yumei Ning, Shilin Fang, Runan Zhang, Jun Fang, Kun Lin, Yang Ding, Haihang Nie, Jingkai Zhou, Qiu Zhao, Hengning Ke, Haizhou Wang, Fan Wang
International Immunopharmacology.2024; 142: 113244. CrossRef

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Genomic and Transcriptomic Characterization of Gastric Cancer with Bone Metastasis: Sujin Oh, Soo Kyung Nam, Keun-Wook Lee, Hye Seung Lee, Yujun Park, Yoonjin Kwak, Kyu Sang Lee, Ji-Won Kim, Jin Won Kim, Minsu Kang, Young Suk Park, Sang-Hoon Ahn, Yun-Suhk Suh, Do Joong Park, Hyung Ho Kim; Cancer Res Treat. 2024;56(1):219-237. Published online August 11, 2023; DOI: https://doi.org/10.4143/crt.2023.340

Abstract PDF Supplementary Material PubReader ePub

Purpose
Bone metastasis (BM) adversely affects the prognosis of gastric cancer (GC). We investigated molecular features and immune microenvironment that characterize GC with BM compared to GC without BM.
Materials and Methods
Targeted DNA and whole transcriptome sequencing were performed using formalin-fixed paraffin-embedded primary tumor tissues (gastrectomy specimens) of 50 GC cases with distant metastases (14 with BM and 36 without BM). In addition, immunohistochemistry (IHC) for mucin-12 and multiplex IHC for immune cell markers were performed.
Results
Most GC cases with BM had a histologic type of poorly cohesive carcinoma and showed worse overall survival (OS) than GC without BM (p < 0.05). GC with BM tended to have higher mutation rates in TP53, KDR, APC, KDM5A, and RHOA than GC without BM. Chief cell-enriched genes (PGA3, PGC, and LIPF), MUC12, MFSD4A, TSPAN7, and TRIM50 were upregulated in GC with BM compared to GC without BM, which was correlated with poor OS (p < 0.05). However, the expression of SERPINA6, SLC30A2, PMAIP1, and ITIH2 were downregulated in GC with BM. GC with BM was associated with PIK3/AKT/mTOR pathway activation, whereas GC without BM showed the opposite effect. The densities of helper, cytotoxic, and regulatory T cells did not differ between the two groups, whereas the densities of macrophages were lower in GC with BM (p < 0.05).
Conclusion
GC with BM had different gene mutation and expression profiles than GC without BM, and had more genetic alterations associated with a poor prognosis.

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Multi-gene DNA methylation profiles of tumor suppressor genes for prognostic prediction in gastric cancer
Soo Kyung Nam, Juhyeong Park, Yoonjin Kwak, Chinbayar Batochir, Eun-Bi Kim, Seong-Ho Kong, Do Joong Park, Hyuk-Joon Lee, Han-Kwang Yang, Hye Seung Lee
BMC Cancer.2026;[Epub] CrossRef
Precision treatment of gastrointestinal tumours and liver disease interaction mechanisms based on multi-omics data and microbiome hubs
Bangxing Lin, Shizheng Tong, Chaokai Ba, Xiang Wang
Frontiers in Cellular and Infection Microbiology.2026;[Epub] CrossRef
Microbial Dynamics across Molecular Subtypes and Prognostic Significance of Lactobacillus in Gastric Cancer
Soo Kyung Nam, Juhyeong Park, Sujin Oh, Yoonjin Kwak, Cheol Min Shin, Kyoung Un Park, Nak-Jung Kwon, Seong-Ho Kong, Do Joong Park, Hyuk-Joon Lee, Han-Kwang Yang, Hye Seung Lee
Cancer Research and Treatment.2026; 58(3): 824. CrossRef
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Ahmad Dawalibi, Mohamad Bakir, Khalid S. Mohammad
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TSPAN7 inhibits pancreatic cancer progression by suppressing DNA double-strand break repair and enhances sensitivity to immunochemotherapy
Hai Lin, Jiancong Zhou, Yaning Li, Lisi Luo, Yan Zeng, Xinyue Liang, Jiaping Yu, Chengying Ye, Pengfei Yang, Yujing Lin, Yufang Li, Linjuan Zeng
Biochemical Pharmacology.2025; 242: 117199. CrossRef
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QingShui Wang, ShengZhao Li, YiNing Xu, Yuluo Chen, Chao Xu, QiuYan He, Yan Ye, YiMin Huang, Yue Wu, KeJia Guo, YaJuan Wei, Yide Huang, Yan Liu, Qing Lin, Shanshan Wang, Feng Li, Minghan Huang, FangQin Xue, Yao Lin
World Journal of Surgical Oncology.2025;[Epub] CrossRef
Migrasome-Related Prognostic Genes in Gastric Cancer: A Transcriptomic and Immunotherapeutic Analysis
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Liudmila V. Spirina, Alexandra V. Avgustinovich, Olga V. Bakina, Sergey G. Afanas’ev, Maxim Yu. Volkov, Sergey V. Vtorushin, Irina V. Kovaleva, Tatyana S. Klyushina, Igor O. Munkuev
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Xi Cao, Yongchao Luo, Songjie Shen, Xinyu Ren
Oncology Letters.2024;[Epub] CrossRef

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Sarcoma

Real-World Clinical Outcomes and Prognostic Factors for Patients with Advanced Angiosarcoma who Received Systemic Treatment: Changhee Park, Miso Kim, Yoonjin Kwak, Kyung Chul Moon, Se Hyun Kim, Bhumsuk Keam, Yu Jung Kim, Tae Min Kim, Dong-Wan Kim; Cancer Res Treat. 2021;53(4):1195-1203. Published online February 1, 2021; DOI: https://doi.org/10.4143/crt.2020.1337

Abstract PDF Supplementary Material PubReader ePub

Purpose
Angiosarcoma is a highly aggressive mesenchymal tumor. Although systemic chemotherapy is often considered for the inoperable or metastatic angiosarcoma, the outcome of such treatment is unsatisfactory and poorly delineated.
Materials and Methods
We reviewed electronic medical records of 75 patients with angiosarcoma who were treated with systemic chemotherapy for inoperable or metastatic disease. Patients were classified as having liver involvement if they had either primary or metastatic hepatic lesions.
Results
Among the patients evaluated, 51 patients were male (68%) and 24 patients (32%) had primary cutaneous angiosarcoma. Liver involvement was present in 28 patients (37.3%). A total of 59 patients received first-line weekly paclitaxel (wPac) and showed an objective response rate (ORR) of 23.7% (n=14), a median progression free survival (mPFS) of 4.0 months (95% confidence interval [CI] 3.0–6.1), and a median overall survival (mOS) of 10.2 months (95% CI 7.0–14.6). Among patients without liver involvement, patients receiving wPac (n=35) had significantly prolonged mPFS (5.8 vs. 3.2 months, respectively, p=0.014) with a tendency for prolonged mOS (13.8 vs. 11.6 months, respectively, p=0.13) than those receiving other regimens (n=12). A total of 24 patients received second- or later-line pazopanib monotherapy and showed an ORR of 16.7% (n=4), a mPFS of 2.4 months (95% CI 1.8–4.3) and a mOS of 5.4 months (95% CI 3.5–NA).
Conclusion
Treatment with first-line wPac and later-line pazopanib seems to provide survival benefit, especially for patients with advanced angiosarcoma without liver involvement.

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Ruolin Lyu, Hongyang Shu, Xiaofan Wu, Yiwen Liu, Ming Wang
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PD-L1 Testing in Gastric Cancer by the Combined Positive Score of the 22C3 PharmDx and SP263 Assay with Clinically Relevant Cut-offs: Yujun Park, Jiwon Koh, Hee Young Na, Yoonjin Kwak, Keun-Wook Lee, Sang-Hoon Ahn, Do Joong Park, Hyung-Ho Kim, Hye Seung Lee; Cancer Res Treat. 2020;52(3):661-670. Published online January 10, 2020; DOI: https://doi.org/10.4143/crt.2019.718

Abstract PDF Supplementary Material PubReader ePub

Purpose
We provide a comparison between 22C3 pharmDx and SP263 assay, for evaluating programmed death ligand 1 (PD-L1) expression in advanced gastric cancer (GC) patients.
Materials and Methods
The PD-L1 immunohistochemistry by 22C3 pharmDx and SP263 assays was performed in the center of the tumor (CT) and invasive margin (IM) in 379 GC tissues using tissue microarrays and interpreted as combined positive score (CPS) and tumor proportion score (TPS). Of the total samples, 55 samples were independently reviewed by five pathologists.
Results
The two assays showed a high correlation in both the CPS and TPS. At a CPS ≥ 1 cut-off, 219 (57.8%) and 231 (60.9%) GCs were positive for PD-L1 with the 22C3 and SP263 assays, and at ≥ 10 cut-off, 37 (9.8%) and 36 (9.5%) GCs were positive, respectively. The overall percent agreement (OPA) was greater than 90% with CPS ≥ 1 and ≥ 10 cut-offs, and TPS ≥ 1% and ≥ 10% cut-offs. There was higher OPA between the two assays with a CPS cut-off ≥ 10 (99.2%) than ≥ 1 (94.7%). The percent agreement between the CT and IM was higher with a CPS cut-off ≥ 10 (92.9%) than ≥ 1 (77.6%). Patient with positive expression at CPS ≥ 5 cut-off had a significantly better outcomes in both assays. Interobserver variability among five pathologists was higher than the assay variability.
Conclusion
Two assays for PD-L1 expression in GC showed high agreement. These results provide guidance for selecting eligible patients with GC for pembrolizumab treatment.

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The Relationship Between PD-1 Expression and Metabolic PET/CT Rarameters of Primary Tumor in NSCLC
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Helicobacter pylori is associated with less tumor-infiltrating lymphocytes and a poor prognosis in gastric cancer
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Molecular-targeted Therapy for Precision Medicine in Gastrointestinal Cancer: Advancement in Cancer Targeting Strategies
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Critical insights on real-life PD-L1 histopathological workflow and assessment in esophageal, esophagogastric junction, and gastric carcinoma in Italy
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Programmed Death Ligand-1 Expression in Gastric Cancer Cases in Zambia
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Efficacy of First-Line Nivolumab Plus Chemotherapy in Advanced Gastric Cancer Stratified by PD-L1 Expression: A Real-World Comparison
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Best Practice PD-L1 Staining and Interpretation in Gastric Cancer Using PD-L1 IHC PharmDx 22C3 and PD-L1 IHC PharmDx 28-8 Assays, with Reference to Common Issues and Solutions
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Histological and biomarker landscape of Claudin18.2-positive gastric and gastroesophageal junction cancers: a study of 937 cases
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A Phase 1a/1b Dose Escalation/Expansion Study of the Anti-PD-1 Monoclonal Antibody Nofazinlimab in Chinese Patients with Solid Tumors or Lymphoma
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Adrenal Nodules Detected at Staging CT in Patients with Resectable Gastric Cancers Have a Low Incidence of Malignancy
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Abdominal Computed Tomography Enhanced Image Features under an Automatic Segmentation Algorithm in Identification of Gastric Cancer and Gastric Lymphoma
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Frontiers in Oncology.2021;[Epub] CrossRef
Prediction of TP53 mutations by p53 immunohistochemistry and their prognostic significance in gastric cancer
Hye Jung Hwang, Soo Kyung Nam, Hyunjin Park, Yujun Park, Jiwon Koh, Hee Young Na, Yoonjin Kwak, Woo Ho Kim, Hye Seung Lee
Journal of Pathology and Translational Medicine.2020; 54(5): 378. CrossRef

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High-Throughput Multiplex Immunohistochemical Imaging of the Tumor and Its Microenvironment: Jiwon Koh, Yoonjin Kwak, Jin Kim, Woo Ho Kim; Cancer Res Treat. 2020;52(1):98-108. Published online May 27, 2019; DOI: https://doi.org/10.4143/crt.2019.195

Abstract PDF PubReader ePub

Purpose
The aim of this study was to develop a formalin-fixed paraffin-embedded (FFPE) tissue based multiplex immunochemistry (mIHC) method for high-throughput comprehensive tissue imaging and demonstrate its feasibility, validity, and usefulness.
Materials and Methods
The mIHC protocol was developed and tested on tissue microarray slides made from archived gastric cancer (GC) tissue samples. On a single FFPE slide, cyclic immunochemistry for multiple markers of immune cells and cytokeratin for tumor cells was performed; hematoxylin staining was used for demarcation of nuclei. Whole slides were digitally scanned after each cycle. For interpretation of mIHC results, we performed computer-assisted image analysis using publicly available software.
Results
Using mIHC, we were able to characterize the tumor microenvironment (TME) of GCs with accurate visualization of various immune cells harboring complex immunophenotypes. Spatial information regarding intratumoral and peritumoral TME could be demonstrated by digital segmentation of image guided by cytokeratin staining results. We further extended the application of mIHC by showing that subcellular localization of molecules can be achieved by image analysis of mIHC results.
Conclusion
We developed a robust method for high-throughput multiplex imaging of FFPE tissue slides. The feasibility and adaptability of mIHC suggest that it is an efficient method for in situ single-cell characterization and analysis.

Citations

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Jianchao Wang, Wenfang Zhang, Jiyang Zhang, Chenhui Zhao, Wei Zhang, Menghan Fang, Fangfang Chen, Zhida Wu, Xiaoya Xu, Ziqing Yu, Qiong Zhu, Yi Shi, Dadong Zhang, Xiaofeng Chen, Gang Chen
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Integrative single-cell, spatial, and bulk transcriptomics reveal an FMR1–FTO axis linked to the immune-excluded phenotype in gastric cancer
Chenxi Mao, Miao Zhang, Kangjie Zhou, Yidong Hong, Yiqian Han, Luming Zhao, Mingtong Liang, Jingzhou Zhang, Nan Hu, Fenglei Wu
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Development and internal validation of a multifactorial risk model for predicting disease-free survival in oral squamous cell carcinoma
Anand Ramanathan, Wan Maria Nabillah Ghani, Sarah Sabrina Zakaria, Zakiah Mat Ripen, Saravanan Gopalan, Marzuki Zainal Abidin, Fairuz Abdul Rahman, Rasika Ekanayaka, Joe Poh Sheng Yeong, Craig Joseph, Yi-Hsin Yang, Zuraiza Mohamad Zaini, Samadarani Bogaha
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Rodolfo Montironi, Alessia Cimadamore, Marina Scarpelli, Liang Cheng, Antonio Lopez-Beltran, Gregor Mikuz
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Programmed Death Ligand 1-Expressing Classical Dendritic Cells Mitigate -Induced Gastritis
Du-Min Go, Seung Hyun Lee, Su-Hyung Lee, Sang-Ho Woo, Kibyeong Kim, Kyeongdae Kim, Kyu Seong Park, Jong-Hwan Park, Sang-Jun Ha, Woo Ho Kim, Jae-Hoon Choi, Dae-Yong Kim
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Expression of the immune checkpoint receptors PD-1, LAG3, and TIM3 in the immune context of stage II and III gastric cancer by using single and chromogenic multiplex immunohistochemistry
Yujun Park, An Na Seo, Jiwon Koh, Soo Kyoung Nam, Yoonjin Kwak, Sang-Hoon Ahn, Do Joong Park, Hyung-Ho Kim, Hye Seung Lee
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Fibroblast Growth Factor Receptor 1 (FGFR1) Amplification Detected by Droplet Digital Polymerase Chain Reaction (ddPCR) Is a Prognostic Factor in Colorectal Cancers: Jeong Mo Bae, Xianyu Wen, Tae-Shin Kim, Yoonjin Kwak, Nam-Yun Cho, Hye Seung Lee, Gyeong Hoon Kang; Cancer Res Treat. 2020;52(1):74-84. Published online May 8, 2019; DOI: https://doi.org/10.4143/crt.2019.062

Abstract PDF Supplementary Material PubReader ePub

Purpose
The purpose of this study was to reveal the clinicopathological characteristics and prognostic implications associated with fibroblast growth factor receptor 1 (FGFR1) amplification in colorectal cancers (CRCs).
Materials and Methods
We measured the copy number of FGFR1 by droplet digital polymerase chain reaction (ddPCR), and analyzed the FGFR1 expression by immunohistochemistry, in 764 surgically resected CRCs (SNUH2007 dataset, 384 CRCs; SNUH Folfox dataset, 380 CRCs).
Results
CRCs with ≥ 3.3 copies of the FGFR1 gene were classified as FGFR1 amplified. FGFR1 amplification was found in 10 of the 384 CRCs (2.6%) in the SNUH2007 dataset, and in 28 of the 380 CRCs (7.4%) in the SNUH Folfox dataset. In the SNUH2007 dataset, there was no association between the FGFR1 copy number status and sex, gross appearance, stage, or differentiation. High FGFR1 expression was associated with female sex and KRAS mutation. At the molecular level, FGFR1 amplification was mutually exclusive with BRAF mutation, microsatellite instability, and MLH1 methylation, in both SNUH2007 and SNUH Folfox datasets. Survival analysis revealed that FGFR1 amplification was associated with significantly worse clinical outcome compared with no FGFR1 amplification, in both SNUH2007 and SNUH Folfox datasets. Within the SNUH2007 dataset, CRC patients with high FGFR1 expression had an inferior progression-free survival compared with those with low FGFR1 expression. The FGFR inhibitor, PD173074, repressed the proliferation of a CRC cell line overexpressing FGFR1, but not of cells with FGFR1 amplification.
Conclusion
FGFR1 amplification measured by ddPCR can be a prognostic indicator of poor clinical outcome in patients with CRCs.

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Olga Karatayev, Sarah F. Leibowitz
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FGFR1-amplified colorectal cancer: a distinct prognostic subtype identified through integrated genomic and immunohistochemical profiling
X. Lyu, R. Cai, B. Han, Y. Liu, Y. Zhang, Z. Wu, Y. Cheng, Z. Lin, G. Qin, X. Xie, J. Zhang, W. Zhan, Y. Deng
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Ligand-Independent Epidermal Growth Factor Receptor Overexpression Correlates with Poor Prognosis in Colorectal Cancer: Sumi Yun, Yoonjin Kwak, Soo Kyung Nam, An Na Seo, Heung-Kwon Oh, Duck-Woo Kim, Sung-Bum Kang, Hye Seung Lee; Cancer Res Treat. 2018;50(4):1351-1361. Published online January 17, 2018; DOI: https://doi.org/10.4143/crt.2017.487

Abstract PDF Supplementary Material PubReader ePub

Purpose
Molecular treatments targeting epidermal growth factor receptors (EGFRs) are important strategies for advanced colorectal cancer (CRC). However, clinicopathologic implications of EGFRs and EGFR ligand signaling have not been fully evaluated. We evaluated the expression of EGFR ligands and correlation with their receptors, clinicopathologic factors, and patients’ survival with CRC.
Materials and Methods
The expression of EGFR ligands, including heparin binding epidermal growth factor-like growth factor (HBEGF), transforming growth factor (TGF), betacellulin, and epidermal growth factor (EGF), were evaluated in 331 consecutive CRC samples using mRNA in situ hybridization (ISH). We also evaluated the expression status of EGFR, human epidermal growth factor receptor 2 (HER2), HER3, and HER4 using immunohistochemistry and/or silver ISH.
Results
Unlike low incidences of TGF (38.1%), betacellulin (7.9%), and EGF (2.1%), HBEGF expression was noted in 62.2% of CRC samples. However, the expression of each EGFR ligand did not reveal significant correlations with survival. The combined analyses of EGFR ligands and EGFR expression indicated that the ligands‒/EGFR+ group showed a significant association with the worst disease-free survival (DFS; p=0.018) and overall survival (OS; p=0.005). It was also an independent, unfavorable prognostic factor for DFS (p=0.026) and OS (p=0.007). Additionally, HER4 nuclear expression, regardless of ligand expression, was an independent, favorable prognostic factor for DFS (p=0.034) and OS (p=0.049), by multivariate analysis.
Conclusion
Ligand-independent EGFR overexpression was suggested to have a significant prognostic impact; thus, the expression status of EGFR ligands, in addition to EGFR, might be necessary for predicting patients' outcome in CRC.

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