Cancer Research and Treatment

Original Articles

Clinical Outcomes and Histologic Subtype-Specific Patterns in Oligometastatic Soft Tissue Sarcoma of the Extremities and Trunk Wall: Implications for Curative Local Ablative Therapy: Eunkyu Yang, Han-Soo Kim, Jay Hoon Park, Yongsung Kim, Shinn Kim, Miso Kim, Jeonghwan Youk, Hak Jae Kim, Hyun-Cheol Kang, Ilkyu Han; Received September 9, 2025 Accepted October 29, 2025 Published online October 30, 2025; DOI: https://doi.org/10.4143/crt.2025.983 [Epub ahead of print]

Abstract PDF Supplementary Material: Purpose
Oligometastatic soft tissue sarcoma (STS) may offer the possibility of cure compared with polymetastatic disease, with progression patterns and treatment responses varying across histologic subtypes. This study investigated the clinical characteristics, oncologic outcomes, and histologic subtype-specific features of oligometastatic STS.
Materials and Methods
We reviewed records of 1,243 patients with extremity/trunk STS who underwent curative surgery between 2000 and 2023. Oligometastatic recurrence occurred in 170 (13.6%), 149 of whom received local ablative therapy (LAT). Disease-specific survival (DSS) and progression-free survival (PFS) were analyzed, along with prognostic factors and subtype-specific characteristics.
Results
The median follow-up was 52.5 months. Surgery alone was the most common LAT (71.2%), followed by surgery with radiotherapy, radiotherapy alone, and radiofrequency ablation. The median DSS was 50.0 months (95% confidence interval [CI], 31.5 to 68.5), with a 5-year DSS rate of 45.2%. The median PFS was 12.0 months (95% CI, 7.6 to 16.4), with a 5-year PFS of 28.1%. On multivariate analysis, LAT was independently associated with longer DSS (hazard ratio, 9.629; p < 0.001). Smaller oligometastatic lesion size and adequate local control of the primary tumor were also independently associated with longer DSS. Metastasis-free interval > 6 months independently predicted longer PFS. Histologic subtypes demonstrated distinct clinical behaviors; for example, myxofibrosarcoma had a lower metastatic rate but poorer DSS, whereas synovial sarcoma showed relatively favorable long-term survival.
Conclusion
Oligometastatic STS represents an intermediate disease state in which LAT can provide meaningful survival benefit. Subtype-specific differences in metastatic behavior and survival outcomes would support individualized, multimodal, and potentially curative treatment strategies.

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Proteomic Analysis Identifies Association of Periostin, a Matricellular Protein, with High Tumor Stroma and Immune Exclusion in Triple-Negative Breast Cancer: Yeonjin Jeon, GunHee Lee, Byung-Kwan Jeong, Yoon Young Kim, JiSun Kim, Jae Ho Jeong, Kyunggon Kim, Hee Jin Lee; Received February 6, 2025 Accepted July 25, 2025 Published online July 28, 2025; DOI: https://doi.org/10.4143/crt.2025.145 [Epub ahead of print]

Abstract PDF Supplementary Material PubReader ePub

Purpose
Immune-excluded/desert tumors show reduced responsiveness to immunotherapy compared to inflamed tumors. The tumor stroma contributes to immune evasion. This study aimed to identify proteins overexpressed in tumors with high tumor stroma among immune excluded triple-negative breast cancer (TNBC) to better understand the mechanisms of immune exclusion.
Materials and Methods
Proteomic analysis was conducted on formalin-fixed, paraffin-embedded samples from 403 cases of TNBC. We compared protein expression between stroma-high versus stroma-low within the immune-excluded subtype. We investigated the correlations between the identified protein expression and other clinicopathologic features. Immunohistochemical (IHC) staining and single-cell analysis were conducted, along with survival analysis.
Results
Among the 247 eligible cases, 81 (32.8%) were classified as immune-excluded and 166 (67.2%) as inflamed. Within the excluded subtype, periostin was the only extracellular matrix-related protein significantly overexpressed in stroma-high cases. Periostin expression demonstrated a positive correlation with the amount of stroma (r=0.51, p < 0.001) and a negative correlation with tumor-infiltrating lymphocytes (TILs) (r=−0.30, p < 0.001). Periostin expression in the tumor stroma was confirmed by IHC. Single-cell analysis demonstrated that periostin originated from cancer-associated fibroblasts (CAFs). High periostin levels correlated with poorer recurrence-free survival (hazard ratio, 1.422; p=0.005).
Conclusion
Periostin is overexpressed in stroma-rich, immune-excluded TNBC and is derived from CAFs. Its expression is associated with reduced TILs and poor prognosis. The development of targeted agents against periostin-positive CAFs may help overcome immune evasion and improve the effectiveness of immunotherapy in TNBC.

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POSTN+ cancer-associated fibroblasts promote bladder cancer progression via angiogenesis and immune modulation: an analysis based on single-cell Transcriptomics
Qun Zhang, Bo Zhang, Jirui Niu, Shiheng Sun
Integrative Biology.2026;[Epub] CrossRef

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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; Received April 25, 2025 Accepted July 16, 2025 Published online July 17, 2025; DOI: https://doi.org/10.4143/crt.2025.449 [Epub ahead of print]

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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Lung and Thoracic cancer

The Feasibility of Using Biomarkers Derived from Circulating Tumor DNA Sequencing as Predictive Classifiers in Patients with Small-Cell Lung Cancer: Yu Feng, Yutao Liu, Mingming Yuan, Guilan Dong, Hongxia Zhang, Tongmei Zhang, Lianpeng Chang, Xuefeng Xia, Lifeng Li, Haohua Zhu, Puyuan Xing, Hongyu Wang, Yuankai Shi, Zhijie Wang, Xingsheng Hu; Cancer Res Treat. 2022;54(3):753-766. Published online October 5, 2021; DOI: https://doi.org/10.4143/crt.2021.905

Abstract PDF Supplementary Material PubReader ePub

Purpose
To investigate the feasibility of biomarkers based on dynamic circulating tumor DNA (ctDNA) to classify small cell lung cancer (SCLC) into different subtypes.
Materials and Methods
Tumor and longitudinal plasma ctDNA samples were analyzed by next-generation sequencing of 1,021 genes. PyClone was used to infer the molecular tumor burden index (mTBI). Pre-treatment tumor tissues [T1] and serial plasma samples were collected (pre-treatment [B1], after two [B2], six [B3] cycles of chemotherapy and at progression [B4]).
Results
Overall concordance between T1 and B1 sequencing (n=30) was 66.5%, and 89.5% in the gene of RB1. A classification method was designed according to the changes of RB1 mutation, named as subtype Ⅰ (both positive at B1 and B2), subtype Ⅱ (positive at B1 but negative at B2), and subtype Ⅲ (both negative at B1 and B2). The median progressive-free survival for subtype Ⅰ patients (4.5 months [95%CI: 2.6-5.8]) was inferior to subtype Ⅱ (not reached, p<0.0001) and subtype Ⅲ (10.8 months [95%CI: 6.0-14.4], p=0.002). The median overall survival for subtype Ⅰ patients (16.3 months [95%CI: 5.3-22.9]) was inferior to subtype Ⅱ (not reached, p=0.01) and subtype Ⅲ (not reached, p=0.02). Patients with a mTBI dropped to zero at B2 had longer median overall survival (not reached vs. 19.5 months, p=0.01). The changes of mTBI from B4 to B1 were sensitive to predict new metastases, with a sensitivity of 100% and a specificity of 85.7%.
Conclusion
Monitoring ctDNA based RB1 mutation and mTBI provided a feasible tool to predict the prognosis of SCLC.

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Dynamic Surveillance of Minimal Residual Disease via a Tumor-Informed Circulating Tumor DNA Assay for Outcome Prediction in Small-Cell Lung Cancer: An Exploratory Pilot Study
Qiuyi Zhang, Die Dai, Yikun Yang, Lihong Guo, Jiesheng Su, Shiqi Lyu, Suni Huang, Meng Zhang, Jianhua Chang
Biomedicines.2026; 14(5): 972. CrossRef
Cell-free and extrachromosomal DNA profiling of small cell lung cancer
Roya Behrouzi, Alexandra Clipson, Kathryn L. Simpson, Fiona Blackhall, Dominic G. Rothwell, Caroline Dive, Florent Mouliere
Trends in Molecular Medicine.2025; 31(1): 64. CrossRef
New insight in early detection and precision medicine in small cell lung cancer: liquid biopsy as innovative clinical tool
Sara Santamaria, Barbara Cardinali, Matteo Rovere, Silvia Marconi, Simone Nardin, Gianluca Sacco, Lucrezia Barcellini, Lucia Del Mastro, Carlo Genova, Simona Coco
Critical Reviews in Clinical Laboratory Sciences.2025; 62(6): 404. CrossRef
Liquid biopsy in diagnosis and monitoring of treatment efficacy in patients with small cell lung cancer
Natalia Galant, Anna Grenda, Paweł Krawczyk, Mateusz Pięt, Janusz Milanowski
Molecular Biology Reports.2025;[Epub] CrossRef
Intercalated Avelumab plus platinum-based chemotherapy in patients with Extensive-Stage Small-Cell Lung cancer (PAVE): Final outcome, immunophenotypic and biomarker analysis of a multi-center phase II Hellenic Cooperative Oncology Group study
Helena Linardou, Kyriaki Papadopoulou, Nikolaos Korfiatis, Anna Goussia, Epaminondas Samantas, Gerasimos Aravantinos, Athina Christopoulou, Nikolaos Spathas, Elena Fountzilas, Amanda Psyrri, Georgia-Angeliki Koliou, Soultana Meditskou, Epaminondas Kosmas,
European Journal of Cancer.2025; 228: 115660. CrossRef
State of the art in treatment of small cell lung cancer
Roya Behrouzi, Fiona Blackhall
Therapeutic Advances in Medical Oncology.2025;[Epub] CrossRef
Circulating tumor DNA as liquid biopsy in lung cancer: Biological characteristics and clinical integration
Changshu Li, Jun Shao, Peiyi Li, Jiaming Feng, Jingwei Li, Chengdi Wang
Cancer Letters.2023; 577: 216365. CrossRef
Prognostic and predictive impact of molecular tumor burden index in non‐small cell lung cancer patients
Fan Yang, Min Tang, Liang Cui, Jing Bai, Jiangyong Yu, Jiayi Gao, Xin Nie, Xu Li, Xuefeng Xia, Xin Yi, Ping Zhang, Lin Li
Thoracic Cancer.2023; 14(31): 3097. CrossRef
Genomic and Gene Expression Studies Helped to Define the Heterogeneity of Small-Cell Lung Cancer and Other Lung Neuroendocrine Tumors and to Identify New Therapeutic Targets
Ugo Testa, Elvira Pelosi, Germana Castelli
Onco.2022; 2(3): 186. CrossRef

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BCL2 Regulation according to Molecular Subtype of Breast Cancer by Analysis of The Cancer Genome Atlas Database: Ki-Tae Hwang, Kwangsoo Kim, Ji Hyun Chang, Sohee Oh, Young A Kim, Jong Yoon Lee, Se Hee Jung, In Sil Choi; Cancer Res Treat. 2018;50(3):658-669. Published online July 4, 2017; DOI: https://doi.org/10.4143/crt.2017.134

Abstract PDF Supplementary Material PubReader ePub

Purpose
We investigated B-cell lymphoma 2 (BCL2) regulation across DNA, RNA, protein, and methylation status according to molecular subtype of breast cancer using The Cancer Genome Atlas (TCGA) database.
Materials and Methods
We analyzed clinical and biological data on 1,096 breast cancers from the TCGA database. Biological data included reverse phase protein array (RPPA), mRNA sequencing (mRNA-seq), mRNA microarray, methylation, copy number alteration linear, copy number alteration nonlinear, and mutation data.
Results
The luminal A and luminal B subtypes showed upregulated expression of RPPA and mRNAseq and hypomethylation compared to the human epidermal growth factor receptor 2 (HER2) and triple-negative subtypes (all p < 0.001). No mutations were found in any subjects. High mRNA-seq and high RPPA were strongly associated with positive estrogen receptor, positive progesterone receptor (all p < 0.001), and negative HER2 (p < 0.001 and p=0.002, respectively). Correlation analysis revealed a strong positive correlation between protein and mRNA levels and a strong negative correlation between methylation and protein and mRNA levels (all p < 0.001). The high BCL2 group showed superior overall survival compared to the low BCL2 group (p=0.006).
Conclusion
The regulation of BCL2 was mainly associated with methylation across the molecular subtypes of breast cancer, and luminal A and luminal B subtypes showed upregulated expression of BCL2 protein, mRNA, and hypomethylation. Although copy number alteration may have played a minor role, mutation status was not related to BCL2 regulation. Upregulation of BCL2 was associated with superior prognosis than downregulation of BCL2.

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Unraveling hereditary breast cancer susceptibility: a systems biology approach on GEO datasets with functional genomic insights and implications for traditional Chinese medicine
Elham Amjad, Babak Sokouti
Egyptian Journal of Medical Human Genetics.2025;[Epub] CrossRef
AL16ALA-SOD2 polymorphism predicts recurrence risk of breast cancer in patients treated with adjuvant tamoxifen
Maiquidieli Dal Berto, Laura Martin Manfroi, Aniúsca Vieira dos Santos, Giovana Tavares dos Santos, Gabriela Krüger da Costa, Camila Macedo Boaro, Péttala Rigon, Rafael José Vargas Alves, Claudia Giuliano Bica
Advances in Cancer Biology - Metastasis.2023; 8: 100108. CrossRef
Clinicopathological features and prognosis of patients with HER2-low breast cancer
Xin Yang, Yao Li, Xu lu, Xiaotian Ren, Bin Hua
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Locoregional Recurrence by Tumor Biology in Breast Cancer Patients after Preoperative Chemotherapy and Breast Conservation Treatment: Eunjin Jwa, Kyung Hwan Shin, Ja Young Kim, Young Hee Park, So-Youn Jung, Eun Sook Lee, In Hae Park, Keun Seok Lee, Jungsil Ro, Yeon-Joo Kim, Tae Hyun Kim; Cancer Res Treat. 2016;48(4):1363-1372. Published online February 18, 2016; DOI: https://doi.org/10.4143/crt.2015.456

Abstract PDF PubReader ePub

Purpose
The purpose of this study is to determine whether breast cancer subtype can affect locoregional recurrence (LRR) and ipsilateral breast tumor recurrence (IBTR) after neoadjuvant chemotherapy (NAC) and breast-conserving therapy (BCT). Materials and Methods We evaluated 335 consecutive patients with clinical stage II-III breast cancer who received NAC plus BCT from 2002 to 2009. Patients were classified according to six molecular subtypes: luminal A (hormone receptor [HR]+/HER2–/Ki-67 < 15%, n=113), luminal B1 (HR+/HER2–/Ki-67 ≥ 15%, n=33), luminal B2 (HR+/HER2+, n=83), HER2 with trastuzumab (HER2[T+]) (HR–/HER2+/use of trastuzumab, n=14), HER2 without trastuzumab (HER2[T–]) (HR–/HER2+, n=31), and triple negative (TN) (HR–/HER2–, n=61).
Results
After a median follow-up period of 7.2 years, 26 IBTRs and 37 LRRs occurred. The 5-year LRR-free survival rates were luminal A, 96.4%; B1, 93.9%; B2, 90.3%; HER2(T+), 92.9%; HER2(T–), 78.3%; and TN, 79.6%. The 5-year IBTR-free survival rates were luminal A, 97.2%; B1, 93.9%; B2, 92.8%; HER2(T+), 92.9%; HER2(T–), 89.1%; and TN, 84.6%. In multivariate analysis, HER2(T–) (IBTR: hazard ratio, 4.2; p=0.04 and LRR: hazard ratio, 7.6; p < 0.01) and TN subtypes (IBTR: hazard ratio, 6.9; p=0.01 and LRR: hazard ratio, 8.1; p < 0.01) were associated with higher IBTR and LRR rates. A pathologic complete response (pCR) was found to show correlation with better LRR and a tendency toward improved IBTR controls in TN patients (IBTR, p=0.07; LRR, p=0.03). Conclusion The TN and HER2(T–) subtypes predict higher rates of IBTR and LRR after NAC and BCT. A pCR is predictive of improved IBTR or LRR in TN subtype.

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Kelly K. Hunt, Vera J. Suman, Hannah F. Wingate, A. Marilyn Leitch, Gary Unzeitig, Judy C. Boughey, Funda Meric-Bernstam, Matthew J. Ellis, John Olson
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Matthew R. Woeste, Neal Bhutiani, Marilyn Donaldson, Kelly M. McMasters, Nicolás Ajkay
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Case Report

Case Series of Different Onset of Skin Metastasis According to the Breast Cancer Subtypes: Junhyeon Cho, Yohan Park, Jong-Chan Lee, Woo Jin Jung, Soohyeon Lee; Cancer Res Treat. 2014;46(2):194-199. Published online April 15, 2014; DOI: https://doi.org/10.4143/crt.2014.46.2.194

Abstract PDF PubReader ePub

We report on five cases of skin metastasis according to the breast cancer (BC) subtype. Two cases of HER2 positive BC showed only skin metastasis after immediate postoperative period and rapid clinical response to targeted therapy. Another two cases of triple negative BC showed thyroid and lung metastasis in addition to skin metastasis, and their response of cytotoxic chemotherapy was not definite. The other hormone positive BC showed skin metastasis only, with a longer, slower, less progressive pattern than other subtypes. Most cases of skin metastasis were detected at terminal stage of malignancy and were considered to have a limited survival period. However, some BC patients can survive longer if the targeted agents are effective. Therefore, physicians should provide detailed follow up of BC after curative treatment and understand the metastatic pattern of BC according to the subtype.

Citations

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Original Articles

Immunohistochemical Expression of Keratin Subtypes in Tumors of Uterine Cervix: Keun Hong Kee, Sung Chul Lim; J Korean Cancer Assoc. 1995;27(4):637-646.

Abstract PDF: Keratin is a major class of intermediate filaments in epithelial cells, and comprises a group of at least 20 different multigene-derived proteins. It is expressed in different epithelia with specific combinations. The materials for this study consisted of chronic cervicitis, reserve cell hyperplasias, squamous metaplasias, cervical intraepithelial neoplasias, squamous cell carcinomas, and adenocarcinomas. All cases were performed by immunohistochemical stains for panel of monoclonal cytokerain(CK) antibodies. Also, some cases were examined by immunoelectron microscopy. The basal cells of exocervix were positively stained for CK 5/6, 8, 14, 18 and 19. The intermediate and superficial cells of exocervix were positive for CK 1, 5/6, 7, 8, 13 and 18. The endocervical columnar cells were positive for CK 7, 8, 18 and 19. The reserve cells were positively stained for CK 5/6, 8, 14, 18 and 19. The metaplastic cells were positively stained for CK 1, 5/6, 7, 8, 10 and 18. The dysplastic cells were positively stained for CK 5/6, 10, 13, l4, 18 and 19. The keratinizing squamous cell carcinomas were positively stained for CK 5/6, 8, 14 and 19. The nonkeratinizing squamous cell carcinomas were positively stained for CK 1, 5/6, 10, 13, 14 and 19. The adenocarcinomas were positively stained for CK 5/6, 7, 8, 10, 14, 18 and 19. In conclusion, individual normal epithelial cells and numerous tumor cells of the uterine cervix have two or more different subtypes of keratin. Keratinizing squamous cell carcinomas show similar staining pattern to those of reserve cells or basal cells. The cytokeratin subtypes of dysplastic cells are similar to those of nonkeratinizing squamous cell carcinomas.

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Subtypes of Epstein - Barr Virus in Malignant Lymphoma in Korea: Kyung Eun Choi, Eun Yoon Cho, Chan Kum Park, Won Keun Lee, Young Hyeh Ko; J Korean Cancer Assoc. 1998;30(2):338-349.

Abstract PDF: PURPOSE
Epstein-Barr virus(EBV) exists in the human population in two genetic forms, usually referred to as type 1 and type 2 which have been defined on the basis of sequence divergence in the EBNA-2 and EBNA-3 family genes. In this study, we were intended to investigate whether the subtypes of EBV in malignant lymphoma in Korea were associated with specific disease entities and geographical distribution.
MATERIALS AND METHODS
Biopsy samples obtained from 18 Korean patients with malignant lymphoma including Hodgkin's disease(3 cases), B cell lymphoma(1 case), and NK/T cell lymphoma(14 cases) were analyzed to determine the subtype of EBV infected therein. DNA was extracted from formalin-fixed, paraffin-embeded tissues by ordinary method and specific viral sequences were sought using the polymerase chain reaction(PCR) and Southern blot hybridization assay. Oligonucleotide primers used for examination of EBV strain type were derived from the EBNA-3B and EBNA-3C coding regions. As a control, four cases of reactive hyperplasia were analyzed.
RESULTS
The two of four reactive hyperplasia cases were associated with type 1 and the rest of two cases with both types. Among the 18 cases with malignant lymphoma, thirteen cases(72%) had type 1, one(6%) had type 2, and four(22%) had dual infections with both types. In case of NK/T cell lymphoma(14 cases) occupying 78% of 18 biopsy samples, 86%(12 cases) were associated with type 1, 7%(1 case) with type 2, and 7%(1 case) with both types. In case of Hodgkin's disease, all of three cases had both types. B cell lymphoma taking only one case of twenty two cases was determined as type 1.
CONCLUSION
These observations indicated that type 1 EBV was predominant in Korean patients with malignant lymphoma, especially NK/T cell lymphoma and showed high frequency of dual viral infections(22%) in Hodgkin's disease as well as in reactive hyperplasia.

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Expression of Keratin Subrypes in Lung Tumprs: Keun Hong Kee, Chan Guk Park, Cheol Hee Choi; J Korean Cancer Assoc. 1996;28(3):490-502.

Abstract PDF: Keratin is a major class of epithelial intermediate filaments, and comprises a group at least 20 different multigene derived proteins. It is expressed in different epithelia with specific combinations. Polyclonal and monoclonal antibodies to cytokeratin(CK) polypeptides were used to study the expression in normal, squamous metaplasia, reserve cell hyperplasia, and neoplastic epithelium of the respiratory tract. All cases were performed of immunohistochemical stain for panel of monoclonal cytokerain antibodies. Also, some cases were examined by electron and immunoelectron microscopy. The squamous papillomas were positive for CK 1, 5/6, 8, 10 and 17. Dysplastic cells were positive for CK 1, 13, 14, and 19. Well differentaited squamous cell carcinomas were reactive for CK 1, 5/6, 13, 14 and 17. Poorly differentiated squamous cell carcinomas were reactive for CK 5/6, 8, 10 and 19. Small cell carcinomas were negative for all keratin subtypes. Adenocarcinomas are reactive for CK 7, 8, 18 and 19. CK 20 is exceptionally negative in all cases. Immunoelectron microscopic examination shows localized gold particles in intermediate filaments and tonofilaments of normal or tumor cells. In conclusion, keratin subtypes of well differentiated squamous cell carcinoma is similar to those of metaplastic cells of the bronchial epithelium and dysplastic cells, while keratin subtypes of poorly differentiated squamous cell carcinoma resembles those of hyperplastic reserve cells and squamous papilloma. It is thought that the application af cykokeratin panel can indicate the degree of differentiation of tumors and distinguish the main subtypes of lung cancer. In addition,immunoelectron microscopic examination is helpful to lo- calization of keratin filaments and diagnosis of epithelial tumors.

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