Spatial heterogeneity of FGFR2b in gastric cancer: a comparative analysis of primary tumors and peritoneal dissemination

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.