Abstract
BACKGROUND: FGFR2b is a new emerging therapeutic target in gastric cancer (GC). This study aimed to examine the clinicopathological characteristics of FGFR2b and its relationship with key biomarkers in locally advanced (LA) and metastatic or unresectable (MU) GC. METHODS: FGFR2b immunohistochemistry (IHC) (FPR2-D) positivity was defined as 2 or 3+ in any tumor cells. Additional tests included IHC for CLDN18.2 (43-14 A), HER2, PD-L1 (22C3), microsatellite instability testing, and Epstein-Barr virus ISH. RESULTS: Of the 1331 patients, 39 (2.9%) and 25 (1.9%) had FGFR2b-positive GC in any % and in ≥10% of tumor cells, respectively. A higher FGFR2b-positivity rate was significantly associated with MU GC and a shorter interval between tumor acquisition and FGFR2b testing. HER2, PD-L1, and CLDN18.2 positivity rates did not differ by FGFR2b status. Intratumoral heterogeneity was observed in 88.0% of FGFR2b-positive resected cases. FGFR2b-positive GC had a trend toward shorter overall survival regardless of clinical factors. CONCLUSION: FGFR2b positivity was higher in MU GC and in GC samples with shorter storage periods. However, no significant association was observed between FGFR2b expression and other key biomarkers or survival outcomes.