{"title":"Spatial heterogeneity of FGFR2b in gastric cancer: a comparative analysis of primary tumors and peritoneal dissemination.","authors":"Haruki Ogawa, Hiroyuki Abe, Koichi Yagi, Yoshifumi Baba, Yasuyuki Seto, Tetsuo Ushiku","doi":"10.1007/s00428-025-04233-z","DOIUrl":null,"url":null,"abstract":"<p><p>Gastric cancer with peritoneal dissemination (PD) confers poor prognosis and limited treatment options. FGFR2b-targeted therapy has emerged as a potential approach for FGFR2b-positive tumors. However, the expression and amplification status of FGFR2b in PD remains poorly characterized. This study aimed to investigate FGFR2b expression and gene amplification in matched primary tumors and PD tissues from gastric cancer patients, and to evaluate their association with established biomarkers including HER2, CLDN18, and PD-L1. Immunohistochemistry (IHC) for FGFR2b was performed on matched primary and PD tissues from 84 patients. FGFR2 FISH was conducted in IHC-positive cases. FGFR2b expression was detected in 7.1% (6/84) of primary tumors and 4.8% (4/84) of PD samples. Expression was highly heterogeneous; only one case was FGFR2b-positive in both primary and PD tissues. FGFR2 amplification was found in 6 of 10 IHC-positive samples, and not observed in IHC-negative samples. FGFR2b status showed no significant correlation with HER2, CLDN18, or PD-L1. FGFR2b expression in gastric cancer is spatially heterogeneous and discordant between primary tumors and PD. It may be preferable to test both primary tumor and PD tissue, if available, to better identify candidates for FGFR2b-targeted therapy. FGFR2b represents a potential therapeutic target for a subset of PD-positive gastric cancers lacking other biomarker expression.</p>","PeriodicalId":23514,"journal":{"name":"Virchows Archiv","volume":" ","pages":""},"PeriodicalIF":3.1000,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Virchows Archiv","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s00428-025-04233-z","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PATHOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Gastric cancer with peritoneal dissemination (PD) confers poor prognosis and limited treatment options. FGFR2b-targeted therapy has emerged as a potential approach for FGFR2b-positive tumors. However, the expression and amplification status of FGFR2b in PD remains poorly characterized. This study aimed to investigate FGFR2b expression and gene amplification in matched primary tumors and PD tissues from gastric cancer patients, and to evaluate their association with established biomarkers including HER2, CLDN18, and PD-L1. Immunohistochemistry (IHC) for FGFR2b was performed on matched primary and PD tissues from 84 patients. FGFR2 FISH was conducted in IHC-positive cases. FGFR2b expression was detected in 7.1% (6/84) of primary tumors and 4.8% (4/84) of PD samples. Expression was highly heterogeneous; only one case was FGFR2b-positive in both primary and PD tissues. FGFR2 amplification was found in 6 of 10 IHC-positive samples, and not observed in IHC-negative samples. FGFR2b status showed no significant correlation with HER2, CLDN18, or PD-L1. FGFR2b expression in gastric cancer is spatially heterogeneous and discordant between primary tumors and PD. It may be preferable to test both primary tumor and PD tissue, if available, to better identify candidates for FGFR2b-targeted therapy. FGFR2b represents a potential therapeutic target for a subset of PD-positive gastric cancers lacking other biomarker expression.
期刊介绍:
Manuscripts of original studies reinforcing the evidence base of modern diagnostic pathology, using immunocytochemical, molecular and ultrastructural techniques, will be welcomed. In addition, papers on critical evaluation of diagnostic criteria but also broadsheets and guidelines with a solid evidence base will be considered. Consideration will also be given to reports of work in other fields relevant to the understanding of human pathology as well as manuscripts on the application of new methods and techniques in pathology. Submission of purely experimental articles is discouraged but manuscripts on experimental work applicable to diagnostic pathology are welcomed. Biomarker studies are welcomed but need to abide by strict rules (e.g. REMARK) of adequate sample size and relevant marker choice. Single marker studies on limited patient series without validated application will as a rule not be considered. Case reports will only be considered when they provide substantial new information with an impact on understanding disease or diagnostic practice.