Expression of FGFR2b and HER2 in gastric cancer: Implications for targeted therapy selection.

Abstract

e16106 Background: FGFR2b and HER2 are clinically relevant therapeutic targets in gastric cancer (GC), with multiple targeted agents demonstrating efficacy in biomarker-selected patient populations. HER2 testing is well established in routine clinical practice, while FGFR2b has recently emerged as a promising target, particularly for antibody–drug conjugate–based therapies. However, the real-world prevalence of FGFR2b expression and its relationship to HER2 status remain incompletely defined. This study aimed to characterize the expression patterns of FGFR2b and HER2 in a cohort of gastric cancer cases to inform biomarker testing strategies and therapeutic development. Methods: Tissue microarrays from 103 patients with histologically confirmed gastric cancer, were evaluated by immunohistochemistry (IHC). FGFR2b expression was assessed using a validated monoclonal antibody and scored based on membranous staining intensity and extent. FGFR2b positivity was defined as ≥10% of tumor cells exhibiting 2+ or 3+ membranous staining. HER2 status was determined using standard clinical IHC criteria in accordance with established gastric cancer guidelines, with 2+ or 3+ staining considered positive. All cases were independently reviewed by board-certified pathologists to ensure consistency. Results: HER2 positivity was identified in 13.6% (14/103) of gastric cancer cases, consistent with reported prevalence in unselected GC populations. FGFR2b expression was detected in 3.88% (4/103) of cases. The low observed frequency of FGFR2b positivity is likely influenced by the application of stringent scoring thresholds and the limited cohort size, rather than reflecting true biological absence. Co-expression of FGFR2b and HER2 was uncommon, suggesting that these biomarkers define largely distinct therapeutic subsets. No consistent association between biomarker expression and histologic subtype was observed in this cohort. Conclusions: FGFR2b and HER2 identify distinct and potentially actionable subsets of gastric cancer. While HER2 remains a more prevalent biomarker, FGFR2b may define a smaller but clinically relevant population for emerging targeted therapies. The low FGFR2b prevalence observed in this study highlights the importance of standardized assessment criteria and larger, well-powered studies to more accurately define its expression landscape and therapeutic relevance in gastric cancer. These findings underscore the value of comprehensive biomarker profiling in gastric cancer and support further evaluation of FGFR2b and HER2 in larger, clinically annotated cohorts.