Cancer Research and Treatment

Original Articles

Prognostic Performance of the Next-Generation Sequencing-Based Multigene Assay in Early Breast Cancer Patients Treated According to the 21-Gene Assay Results: Eunhye Kang, Jong-Ho Cheun, Jeeyeon Lee, Jiwon Koh, Hyunwoo Lee, Ji-Young Park, Hee Jin Lee, Byeongju Kang, Woong Ki Park, Jeongeun Son, Bumjoon Kim, Woosung Chung, Wonshik Han, Han-Byoel Lee, Sae Byul Lee, Jai Min Ryu; Received October 28, 2024 Accepted December 22, 2024 Published online December 23, 2024; DOI: https://doi.org/10.4143/crt.2024.1035 [Epub ahead of print]

Abstract PDF Supplementary Material PubReader ePub: Purpose
Multigene assays guide treatment decisions in early-stage hormone receptor-positive breast cancer. OncoFREE, a next-generation sequencing assay using 179 genes, was developed for this purpose. This study aimed to evaluate the concordance between the Oncotype DX (ODX) recurrence score (RS) and the OncoFREE Decision Index (DI) and to compare their performance.
Materials and Methods
We retrospectively collected tumor blocks from patients who underwent ODX and treatment between 2012 and 2022 at four tertiary hospitals and performed OncoFREE on these samples. Distant metastasis-free survival (DMFS) was compared using RS and DI, with score cut-offs of 25 and 20, respectively.
Results
Among 838 patients, a strong correlation was observed between RS and DI (Pearson correlation coefficient 0.83). At a median follow-up of 54 months, patients with high DI had significantly worse DMFS compared to those with low-DI (log-rank p < 0.001; hazard ratio [HR], 5.73; 95% confidence interval [CI], 1.87 to 17.57; multivariable p=0.048; HR, 3.45; 95% CI, 1.01 to 11.76). In 513 patients aged ≤ 50 years, DMFS was significantly different as a function of DI (p=0.035; HR, 3.98; 95% CI, 1.00 to 15.89) but not RS (p=0.792). Among 376 patients aged ≤ 50 years who avoided chemotherapy based on low-RS, 64 with high DI had worse DMFS (p=0.015; HR, 5.91; 95% CI, 1.17 to 29.78).
Conclusion
OncoFREE showed strong concordance with ODX and effectively identified high-risk patients, particularly in younger individuals. It could be an affordable alternative to ODX for guiding treatment in hormone receptor-positive early breast cancer.

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Hematologic malignancy

Higher Microbial Abundance and Diversity in Bronchus-Associated Lymphoid Tissue Lymphomas Than in Non-cancerous Lung Tissues: Jung Heon Kim, Jae Sik Kim, Noorie Choi, Jiwon Koh, Yoon Kyung Jeon, Ji Hyun Chang, Eung Soo Hwang, Il Han Kim; Cancer Res Treat. 2025;57(2):580-589. Published online September 30, 2024; DOI: https://doi.org/10.4143/crt.2024.689

Abstract PDF Supplementary Material PubReader ePub: Purpose
It is well known that the majority of the extranodal marginal zone lymphomas of mucosa-associated lymphoid tissues (MALT lymphomas) are associated with microbiota, e.g., gastric MALT lymphoma with Helicobacter pylori. In general, they are very sensitive to low-dose radiotherapy and chemotherapeutic agents. The microbiota profile is not clearly elucidated in bronchus-associated lymphoid tissue (BALT) lymphoma, a rare type of MALT lymphoma in the lung. Thus, this study aimed to clarify the intratumor microbiome in BALT lymphoma using the third-generation next-generation sequencing (NGS) method.
Materials and Methods
DNAs were extracted from 12 formalin-fixed paraffin-embedded (FFPE) tumor tissues obtained from BALT lymphoma patients diagnosed between 1990 and 2016. 16S rRNA gene was amplified by polymerase chain reaction. Amplicons were sequenced using a Nanopore platform. Next-generation sequencing analysis was performed to assess microbial profiles. For comparison, FFPE specimens from nine non-cancerous lung tissues were also analyzed.
Results
Specific bacterial families including Burkholderiaceae, Bacillaceae, and Microbacteriaceae were associated with BALT lymphoma by a linear discriminant analysis effect size approach. Although the number of specimens was limited, BALT lymphomas exhibited significantly higher microbial abundance and diversity with distinct microbial composition patterns and correlation networks than non-cancerous lung tissues.
Conclusion
This study provides the first insight into intratumor microbiome in BALT lymphoma using the third-generation NGS method. A distinct microbial composition suggests the presence of a unique tumor microenvironment of BALT lymphoma.

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Breast cancer

Harnessing Institutionally Developed Clinical Targeted Sequencing to Improve Patient Survival in Breast Cancer: A Seven-Year Experience: Jiwon Koh, Jinyong Kim, Go-Un Woo, Hanbaek Yi, So Yean Kwon, Jeongmin Seo, Jeong Mo Bae, Jung Ho Kim, Jae Kyung Won, Han Suk Ryu, Yoon Kyung Jeon, Dae-Won Lee, Miso Kim, Tae-Yong Kim, Kyung-Hun Lee, Tae-You Kim, Jee-Soo Lee, Moon-Woo Seong, Sheehyun Kim, Sungyoung Lee, Hongseok Yun, Myung Geun Song, Jaeyong Choi, Jong-Il Kim, Seock-Ah Im; Cancer Res Treat. 2025;57(2):443-456. Published online August 21, 2024; DOI: https://doi.org/10.4143/crt.2024.296

Abstract PDF Supplementary Material PubReader ePub: Purpose
Considering the high disease burden and unique features of Asian patients with breast cancer (BC), it is essential to have a comprehensive view of genetic characteristics in this population. An institutional targeted sequencing platform was developed through the Korea Research-Driven Hospitals project and was incorporated into clinical practice. This study explores the use of targeted next-generation sequencing (NGS) and its outcomes in patients with advanced/metastatic BC in the real world.
Materials and Methods
We reviewed the results of NGS tests administered to BC patients using a customized sequencing platform—FiRST Cancer Panel (FCP)—over 7 years. We systematically described clinical translation of FCP for precise diagnostics, personalized therapeutic strategies, and unraveling disease pathogenesis.
Results
NGS tests were conducted on 548 samples from 522 patients with BC. Ninety-seven point six percentage of tested samples harbored at least one pathogenic alteration. The common alterations included mutations in TP53 (56.2%), PIK3CA (31.2%), GATA3 (13.8%), BRCA2 (10.2%), and amplifications of CCND1 (10.8%), FGF19 (10.0%), and ERBB2 (9.5%). NGS analysis of ERBB2 amplification correlated well with human epidermal growth factor receptor 2 immunohistochemistry and in situ hybridization. RNA panel analyses found potentially actionable and prognostic fusion genes. FCP effectively screened for potentially germline pathogenic/likely pathogenic mutation. Ten point three percent of BC patients received matched therapy guided by NGS, resulting in a significant overall survival advantage (p=0.022), especially for metastatic BCs.
Conclusion
Clinical NGS provided multifaceted benefits, deepening our understanding of the disease, improving diagnostic precision, and paving the way for targeted therapies. The concrete advantages of FCP highlight the importance of multi-gene testing for BC, especially for metastatic conditions.

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Case Report

Molecular and Treatment Characteristics of SMARCB1 or SMARCA4-Deficient Undifferentiated Tumor: Retrospective Case Series: Hyeon Gyu Kang, Jiwon Koh, Tae Min Kim, Doo Hee Han, Tae-Bin Won, Dong-Wan Kim, Dong-Young Kim, Bhumsuk Keam; Cancer Res Treat. 2024;56(3):967-971. Published online February 13, 2024; DOI: https://doi.org/10.4143/crt.2023.1308

Abstract PDF PubReader ePub: SMARCB1 or SMARCA4-deficient sinonasal carcinoma or thoracic undifferentiated tumor has aggressive nature with a poor prognosis. Patients with this disease were diagnosed by immunohistochemistry or next-generation sequencing. Those who were able to receive a surgery tended to be cured, while the others treated with chemotherapy, radiation therapy, or immune checkpoint inhibitor were often insensitive to these therapies. However, one having CD274 (PD-L1) amplification showed the response to immune checkpoint inhibitor and a good prognosis. We believed that this report could provide promising information for determining the optimal treatment option.

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Original Articles

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.

Citations

Citations to this article as recorded by

PD-L1 as a Biomarker in Gastric Cancer Immunotherapy
Yunjoo Cho, Soomin Ahn, Kyoung-Mee Kim
Journal of Gastric Cancer.2025; 25(1): 177. CrossRef
CT radiomics-based intratumoral and intertumoral heterogeneity indicators for prognosis prediction in gastric cancer patients receiving neoadjuvant chemotherapy
Jiazheng Li, Zhenhui Li, Yinkui Wang, Yuzhuo Li, Jing Zhang, Ziyu Li, Lei Tang
European Radiology.2025;[Epub] CrossRef
Biomarkers in gastroesophageal cancer 2025: an updated consensus statement by the Spanish Society of Medical Oncology (SEOM) and the Spanish Society of Pathology (SEAP)
Maria Alsina Maqueda, Ana Teijo Quintáns, Miriam Cuatrecasas, Maria Jesús Fernández Aceñero, Ana Fernández Montes, Carlos Gómez Martín, Paula Jiménez Fonseca, Carolina Martínez Ciarpaglini, Fernando Rivera Herrero, Mar Iglesias Coma
Clinical and Translational Oncology.2025;[Epub] CrossRef
Treatment Selection for Patients with HER2-Negative Metastatic Gastric Cancer Expressing Claudin 18.2 and PD-L1
Yusuke Miyajima, Takeshi Kawakami
Cancers.2025; 17(7): 1120. CrossRef
Efficacy of the first-line immune checkpoint inhibitor plus chemotherapy for gastroesophageal cancer: A meta-analysis of phase III trials including unreported PD-L1 subgroups
Choong-kun Lee, Sejung Park, Yaeji Lee, Choa Yun, Moonki Hong, Chung Mo Nam, Hyun Cheol Chung, Sun Young Rha
Cancer Letters.2025; 623: 217718. CrossRef
Biomarker-Driven Approaches to Bone Metastases: From Molecular Mechanisms to Clinical Applications
Youssef Elshimy, Abdul Rahman Alkhatib, Bilal Atassi, Khalid S. Mohammad
Biomedicines.2025; 13(5): 1160. CrossRef
Helicobacter pylori is associated with less tumor-infiltrating lymphocytes and a poor prognosis in gastric cancer
Zetian Chen, Zhijun Zhang, Hongxin Huang, Chen Lu, Qingya Li, Mengpei Yan, Chengjun Zhu, Sen Wang, Hongda Liu, Zekuan Xu, Zheng Li
BMC Gastroenterology.2025;[Epub] CrossRef
Neoadjuvant Immunotherapy in Gastroesophageal Cancer: A Promising Early Signal?
Mojun Zhu, Harry H. Yoon
Journal of Clinical Oncology.2024; 42(4): 373. CrossRef
Programmed death ligand-1 (PD-L1) clone 22C3 expression in resected colorectal cancer as companion diagnostics for immune checkpoint inhibitor therapy: A comparison study and inter-rater agreement evaluation across proposed cut-offs and predictive (TPS, C
Dordi Lea, Claudia Zaharia, Kjetil Søreide
Cancer Treatment and Research Communications.2024; 38: 100788. CrossRef
The relationship between high ratios of CD4/FOXP3 and CD8/CD163 and the improved survivability of metastatic triple-negative breast cancer patients: a multicenter cohort study
Jeffry Beta Tenggara, Andhika Rachman, Joedo Prihartono, Lisnawati Rachmadi, Sonar Soni Panigoro, Didik Setyo Heriyanto, Noorwati Sutandyo, Intan Russianna Nasution, Familia Bella Rahadiati, Ricci Steven, Rachelle Betsy, Samuel Juanputra, Aru Wisaksono Su
BMC Research Notes.2024;[Epub] CrossRef
Who Should Receive Immunotherapy for Advanced Gastroesophageal Cancer?
Suhaib Khateeb, Ludimila Cavalcante, Noor Alnairat, Meghana Singh, Ibrahim Halil Sahin, Azhar Saeed, Anwaar Saeed
Current Treatment Options in Oncology.2024; 25(4): 496. CrossRef
Evaluation of PD-L1 Expression in Colorectal Carcinomas by Comparing Scoring Methods and Their Significance in Relation to Clinicopathologic Parameters
Mirela Frančina, Mislav Mikuš, Marin Mamić, Tihomir Jovanović, Mario Ćorić, Božica Lovrić, Ivan Vukoja, Goran Zukanović, Kristijan Matković, Jasmina Rajc, Ferdinand Slišurić, Mateja Jurić-Marelja, Goran Augustin, Ilijan Tomaš
Diagnostics.2024; 14(10): 1007. CrossRef
The tumor immune composition of mismatch repair deficient and Epstein-Barr virus-positive gastric cancer: A systematic review
J. Bos, T.S. Groen-van Schooten, C.P. Brugman, F.S. Jamaludin, H.W.M. van Laarhoven, S. Derks
Cancer Treatment Reviews.2024; 127: 102737. CrossRef
Discordant PD-L1 results between 28–8 and 22C3 assays are associated with outcomes of gastric cancer patients treated with nivolumab plus chemotherapy
Hyung-Don Kim, Jinho Shin, In Hye Song, Jaewon Hyung, Hyungeun Lee, Min-Hee Ryu, Young Soo Park
Gastric Cancer.2024; 27(4): 819. CrossRef
Claudin-18 status and its correlation with HER2 and PD-L1 expression in gastric cancer with peritoneal dissemination
Haruki Ogawa, Hiroyuki Abe, Koichi Yagi, Yasuyuki Seto, Tetsuo Ushiku
Gastric Cancer.2024; 27(4): 802. CrossRef
Interpretation of PD-L1 expression in gastric cancer: summary of a consensus meeting of Korean gastrointestinal pathologists
Soomin Ahn, Yoonjin Kwak, Gui Young Kwon, Kyoung-Mee Kim, Moonsik Kim, Hyunki Kim, Young Soo Park, Hyeon Jeong Oh, Kyoungyul Lee, Sung Hak Lee, Hye Seung Lee
Journal of Pathology and Translational Medicine.2024; 58(3): 103. CrossRef
PD-L1 Immunohistochemistry in Gastric Cancer: Comparison of Combined Positive Score and Tumor Area Positivity Across 28-8, 22C3, and SP263 Assays
Samuel J. Klempner, Eric S. Cowden, Samuel L. Cytryn, Matteo Fassan, Hisato Kawakami, Hideaki Shimada, Laura H. Tang, Daniel-Christoph Wagner, Yasushi Yatabe, Alexander Savchenko, Jennifer Salcius, Dorhyun Johng, Jing Chen, Giuliana Montenegro, Markus Moe
JCO Precision Oncology.2024;[Epub] CrossRef
PD-L1 expression in squamous cervical carcinomas of Mozambican women living with or without HIV
Lucília Lovane, Satish Tulsidás, Carla Carrilho, Christina Karlsson
Scientific Reports.2024;[Epub] CrossRef
First-line immune checkpoint inhibitors in low programmed death-ligand 1-expressing population
Feiyang Zhang, Guoming Chen, Yixin Yin, Xiaojiang Chen, Runcong Nie, Yingbo Chen
Frontiers in Pharmacology.2024;[Epub] CrossRef
Concordance of PD-L1 status in primary gastroesophageal adenocarcinoma and matched peritoneal metastases: a single institution study
V. Massa, F. Signorini, F. Salani, M.E. Filice, G. Grelli, P. Lippolis, P. Faviana, V. Genovesi, S. Santi, C. Vivaldi, S. Cesario, A. Bertolucci, C. Cremolini, V. Nardini, G. Masi, C. Ugolini, L. Fornaro
ESMO Gastrointestinal Oncology.2024; 5: 100089. CrossRef
A Phase 1a/1b Dose Escalation/Expansion Study of the Anti-PD-1 Monoclonal Antibody Nofazinlimab in Chinese Patients with Solid Tumors or Lymphoma
Jifang Gong, Ye Guo, Yanqiao Zhang, Yi Ba, Tong Chen, Wei Li, Caicun Zhou, Mengzhao Wang, Haiyan Yang, Yuhong Zhou, Qiqing Cai, Ziping Wang, Gang Huang, Wei Zhang, Rila Su, Zhongheng Cai, Zenglian Yue, Jinzhou Dou, Peiqi Li, Rachel Wu, Archie N. Tse, Lin
Targeted Oncology.2024; 19(5): 723. CrossRef
Immune checkpoint inhibitors in advanced gastroesophageal adenocarcinoma: a series of patient-level meta-analyses in different programmed death-ligand 1 subgroups
A.G. Leone, A.S. Mai, K.Y. Fong, D.W.T. Yap, K. Kato, E. Smyth, M. Moehler, J.T.C. Seong, R. Sundar, J.J. Zhao, F. Pietrantonio
ESMO Open.2024; 9(11): 103962. CrossRef
HIPEC for Metastatic Gastric Cancer: Moving the Needle Towards 3-Year Survival
Neal Bhutiani, Y. David Seo, Kristen A. Robinson, Michael G. White, Naruhiko Ikoma, Paul F. Mansfield, Jenny J. Li, Mariela Blum Murphy, Jaffer A. Ajani, Brian D. Badgwell
European Journal of Surgical Oncology.2024; : 108790. CrossRef
Biomarkers for Predicting Response to Personalized Immunotherapy in Gastric Cancer
Moonsik Kim, Ji Yun Jeong, An Na Seo
Diagnostics.2023; 13(17): 2782. CrossRef
Development of an automated combined positive score prediction pipeline using artificial intelligence on multiplexed immunofluorescence images
Abhishek Vahadane, Shreya Sharma, Devraj Mandal, Madan Dabbeeru, Josephine Jakthong, Miguel Garcia-Guzman, Shantanu Majumdar, Chung-Wein Lee
Computers in Biology and Medicine.2023; 152: 106337. CrossRef
CT-based delta radiomics in predicting the prognosis of stage IV gastric cancer to immune checkpoint inhibitors
Jiazheng Li, Zifan Chen, Yang Chen, Jie Zhao, Meng He, Xiaoting Li, Li Zhang, Bin Dong, Xiaotian Zhang, Lei Tang, Lin Shen
Frontiers in Oncology.2023;[Epub] CrossRef
Efficacy of PD-1/PD-L1 inhibitors in gastric or gastro-oesophageal junction cancer based on clinical characteristics: a meta-analysis
Gengwei Huo, Wenjie Liu, Peng Chen
BMC Cancer.2023;[Epub] CrossRef
Clinical relevance of PD-1 positive CD8 T-cells in gastric cancer
Joan Choo, Ley Fang Kua, Mu Yar Soe, Bernadette Reyna Asuncion, Benjamin Kye Jyn Tan, Chong Boon Teo, Ryan Yong Kiat Tay, Jimmy So, Asim Shabbir, Kim Guowei, Hon Lyn Tan, Gloria Chan, Haoran Ma, Gokula Krishnan Ramachandran, Jeffrey H. Y. Lum, Cheng Ean C
Gastric Cancer.2023; 26(3): 393. CrossRef
Genetic and immune microenvironment characterization of HER2‐positive gastric cancer: Their association with response to trastuzumab‐based treatment
Hyun Jung Kwon, Yujun Park, Soo Kyung Nam, Enoch Kang, Ka‐Kyung Kim, Inhae Jeong, Yoonjin Kwak, Jeesun Yoon, Tae‐Yong Kim, Keun‐Wook Lee, Do‐Youn Oh, Seock‐Ah Im, Seong‐Ho Kong, Do Joong Park, Hyuk‐Joon Lee, Hyung‐Ho Kim, Han‐Kwang Yang, Hye Seung Lee
Cancer Medicine.2023; 12(9): 10371. CrossRef
High Interobserver Variability Among Pathologists Using Combined Positive Score to Evaluate PD-L1 Expression in Gastric, Gastroesophageal Junction, and Esophageal Adenocarcinoma
Marie E. Robert, Josef Rüschoff, Bharat Jasani, Rondell P. Graham, Sunil S. Badve, Manuel Rodriguez-Justo, Liudmila L. Kodach, Amitabh Srivastava, Hanlin L. Wang, Laura H. Tang, Giancarlo Troncone, Federico Rojo, Benjamin J. Van Treeck, James Pratt, Iryna
Modern Pathology.2023; 36(5): 100154. CrossRef
Heterogeneous distribution pattern of CD3+ tumor-infiltrated lymphocytes (TILs) and high combined positive score (CPS) favored the prognosis of resected early stage small-cell lung cancer
Liang Zhu, Guoping Cheng, Meijuan Wu, Ming Chen, Ying Jin
Translational Oncology.2023; 34: 101697. CrossRef
The Role of Immunotherapy in Esophageal and Gastric Cancer
Hans Dedecker, Laure-Anne Teuwen, Timon Vandamme, Andreas Domen, Hans Prenen
Clinical Colorectal Cancer.2023; 22(2): 175. CrossRef
Tissue- and liquid biopsy-based biomarkers for immunotherapy in breast cancer
Luca Licata, Marco Mariani, Federico Rossari, Giulia Viale, Giulia Notini, Matteo Maria Naldini, Carlo Bosi, Marta Piras, Matteo Dugo, Giampaolo Bianchini
The Breast.2023; 69: 330. CrossRef
PD‐L1andHLA‐class I expression status and their therapeutic implication in oesophageal small‐cell carcinoma
Satoshi Yamashita, Hiroyuki Abe, Hiroharu Yamashita, Koichi Yagi, Yasuyuki Seto, Tetsuo Ushiku
Histopathology.2023; 83(2): 264. CrossRef
Programmed death-ligand 1 expression and overall survival in Thai patients with gastric cancer
Taned Chitapanarux, Pawut Gumrai, Sarawut Kongkarnka, Komson Wannasai, Nirush Lertprasertsuke
Scientific Reports.2023;[Epub] CrossRef
Efficacy of Pd-1/Pd-L1 Inhibitors in Advanced Gastroesophageal Cancer Based on Characteristics: A Meta-Analysis
Wenjie Liu, Gengwei Huo, Peng Chen
Immunotherapy.2023; 15(10): 751. CrossRef
Immunology and immunotherapy in gastric cancer
Xiaqing Xu, Jiaxing Chen, Wenxing Li, Chenlu Feng, Qian Liu, Wenfang Gao, Meng He
Clinical and Experimental Medicine.2023; 23(7): 3189. CrossRef
Targeted Therapies and Developing Precision Medicine in Gastric Cancer
Rille Pihlak, Caroline Fong, Naureen Starling
Cancers.2023; 15(12): 3248. CrossRef
Programmed death ligand 1 (PD-L1) expression in gastric cancer: literature review
T. N. Sotnikova, N. V. Danilova, P. G. Malkov, T. V. Polushkina
Advances in Molecular Oncology.2023; 10(2): 70. CrossRef
Novel Biomarkers of Gastric Cancer: Current Research and Future Perspectives
Yasushi Sato, Koichi Okamoto, Yutaka Kawano, Akinari Kasai, Tomoyuki Kawaguchi, Tamotsu Sagawa, Masahiro Sogabe, Hiroshi Miyamoto, Tetsuji Takayama
Journal of Clinical Medicine.2023; 12(14): 4646. CrossRef
Programmed death-ligand 1 (PD-L1) expression in primary gastric adenocarcinoma and matched metastases
Drolaiz H. W. Liu, Heike I. Grabsch, Beat Gloor, Rupert Langer, Bastian Dislich
Journal of Cancer Research and Clinical Oncology.2023; 149(14): 13345. CrossRef
Chemoimmunotherapy for esophageal squamous cell carcinoma—Summary and discussion of recent clinical trials
Zhen Zhang, Jiaqian Huang, Yuhong Xu, Huiyan Luo
MedComm – Future Medicine.2023;[Epub] CrossRef
Next generation immuno-oncology biomarkers in gastrointestinal cancer: what does the future hold?
Hassan Abushukair, Obada Ababneh, Ayah Al-Bzour, Ibrahim Halil Sahin, Anwaar Saeed
Expert Review of Molecular Diagnostics.2023; 23(10): 863. CrossRef
Impact of programmed death‐ligand 1 (PD‐L1) positivity on clinical and molecular features of patients with metastatic gastric cancer
Minkyue Shin, Soomin Ahn, Jaeyun Jung, Sujin Hyung, Kyoung‐Mee Kim, Seung Tae Kim, Won Ki Kang, Jeeyun Lee
Cancer Medicine.2023; 12(18): 18633. CrossRef
Regulatory T cells in gastric cancer: Key controllers from pathogenesis to therapy
Ion Negura, Mariana Pavel-Tanasa, Mihai Danciu
Cancer Treatment Reviews.2023; 120: 102629. CrossRef
The prognostic value of a combined immune score in tumor and immune cells assessed by immunohistochemistry in triple-negative breast cancer
Ji Eun Choi, Jae Seok Lee, Min-Sun Jin, Ilias P. Nikas, Kwangsoo Kim, Sunah Yang, Soo Young Park, Jiwon Koh, Sohyeon Yang, Seock-Ah Im, Han Suk Ryu
Breast Cancer Research.2023;[Epub] CrossRef
Comparison of SP142 and 22C3 Immunohistochemistry PD-L1 Assays for Clinical Efficacy of Atezolizumab in Non–Small Cell Lung Cancer: Results From the Randomized OAK Trial
Shirish Gadgeel, Fred R. Hirsch, Keith Kerr, Fabrice Barlesi, Keunchil Park, Achim Rittmeyer, Wei Zou, Namrata Bhatia, Hartmut Koeppen, Sarah M. Paul, David Shames, Jing Yi, Christina Matheny, Marcus Ballinger, Mark McCleland, David R. Gandara
Clinical Lung Cancer.2022; 23(1): 21. CrossRef
Adrenal Nodules Detected at Staging CT in Patients with Resectable Gastric Cancers Have a Low Incidence of Malignancy
Hae Young Kim, Won Chang, Yoon Jin Lee, Ji Hoon Park, Jungheum Cho, Hee Young Na, Hyungwoo Ahn, Sung Il Hwang, Hak Jong Lee, Young Hoon Kim, Kyoung Ho Lee
Radiology.2022; 302(1): 129. CrossRef
Immunohistochemistry as predictive and prognostic markers for gastrointestinal malignancies
Matthew W. Rosenbaum, Raul S. Gonzalez
Seminars in Diagnostic Pathology.2022; 39(1): 48. CrossRef
Histopathology of Gastrointestinal Immune-related Adverse Events
M. Lisa Zhang, Vikram Deshpande
American Journal of Surgical Pathology.2022; 46(1): e15. CrossRef
Safety and efficacy of HER2 blockade by trastuzumab-based chemotherapy-containing combination strategies in HER2+ gastroesophageal adenocarcinoma
D.V.T. Catenacci, H.C. Chung, L. Shen, M. Moehler, H.H. Yoon, M.K. Rosales, Y.-K. Kang
ESMO Open.2022; 7(1): 100360. CrossRef
PD-L1 and HER2 expression in gastric adenocarcinoma and their prognostic significance
Jie Lian, Guanjun Zhang, Yun Zhang, Heng Liu, Jiaojiao Zhang, Pengfei Nan, Wei Tian
Digestive and Liver Disease.2022; 54(10): 1419. CrossRef
Tissue miR-200c-3p and circulating miR-1290 as potential prognostic biomarkers for colorectal cancer
Enoch Kang, Sung Cheol Jung, Soo Kyung Nam, Yujun Park, Soo Hyun Seo, Kyoung Un Park, Heung-Kwon Oh, Duck-Woo Kim, Sung-Bum Kang, Hye Seung Lee
Scientific Reports.2022;[Epub] CrossRef
Gastric Cancer: Mechanisms, Biomarkers, and Therapeutic Approaches
Sangjoon Choi, Sujin Park, Hyunjin Kim, So Young Kang, Soomin Ahn, Kyoung-Mee Kim
Biomedicines.2022; 10(3): 543. CrossRef
Immunotherapy use in oesophagogastric cancers—a review of the literature
Annabel Smith, Amitesh Roy, Christos S. Karapetis, Vy Broadbridge, Timothy Price
British Journal of Cancer.2022; 127(1): 21. CrossRef
Interspatial Distribution of Tumor and Immune Cells in Correlation with PD-L1 in Molecular Subtypes of Gastric Cancers
Bastian Dislich, Kirsten D. Mertz, Beat Gloor, Rupert Langer
Cancers.2022; 14(7): 1736. CrossRef
Immunotherapy in Gastro-Oesophageal Cancer: Current Practice and the Future of Personalised Therapy
Mary E. Booth, Elizabeth C. Smyth
BioDrugs.2022; 36(4): 473. CrossRef
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Man Jiang, Chuantao Zhang, Yabin Hu, Tianjun Li, Guangjie Yang, Guanqun Wang, Jingjuan Zhu, Changfeng Shao, Helei Hou, Na Zhou, Kewei Liu, Xiaochun Zhang
The Oncologist.2022; 27(11): e856. CrossRef
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Lihua Zhou, Hao Hu, Lei Zhou, Yi Zhou, Ahmed Faeq Hussein
Computational and Mathematical Methods in Medicine.2022; 2022: 1. CrossRef
Margetuximab with retifanlimab as first-line therapy in HER2+/PD-L1+ unresectable or metastatic gastroesophageal adenocarcinoma: MAHOGANY cohort A
D.V.T. Catenacci, Y.-K. Kang, H.H. Yoon, B.Y. Shim, S.T. Kim, D.-Y. Oh, A.I. Spira, S.V. Ulahannan, E.J. Avery, P.M. Boland, J. Chao, H.C. Chung, F. Gardner, S.J. Klempner, K.-W. Lee, S.C. Oh, J. Peguero, M.B. Sonbol, L. Shen, M. Moehler, J. Sun, D. Li, M
ESMO Open.2022; 7(5): 100563. CrossRef
Advances in molecular biomarkers research and clinical application progress for gastric cancer immunotherapy
Hongzhen Cai, Man Li, Ruiyi Deng, Mopei Wang, Yanyan Shi
Biomarker Research.2022;[Epub] CrossRef
Immune Checkpoint Inhibitors for Gastrointestinal Malignancies: An Update
Kathryn DeCarli, Jonathan Strosberg, Khaldoun Almhanna
Cancers.2022; 14(17): 4201. 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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