Comprehensive analysis of FGFR2b and its correlation with essential biomarkers, intratumoral heterogeneity, and survival in advanced gastric cancer.

Journal: British journal of cancer

This study evaluated FGFR2b protein expression in a large real‑world cohort of 1331 patients with locally advanced or metastatic/unresectable gastric cancer and its relationship with other actionable biomarkers and outcomes.

FGFR2b immunohistochemistry was considered positive when staining was 2+ or 3+ in any tumor cells; a ≥10% tumor cell cutoff was also analyzed. FGFR2b positivity was uncommon: 2.9% of cases were positive at any percentage of tumor cells and 1.9% at the ≥10% threshold.

  • FGFR2b expression patterns: FGFR2b expression was more frequent in metastatic/unresectable disease compared with locally advanced tumors, and positivity was significantly associated with shorter tissue storage time, suggesting antigen degradation over time in archived samples.
  • Association with other biomarkers: FGFR2b status showed no meaningful association with HER2, PD‑L1, CLDN18.2, microsatellite instability, or Epstein–Barr virus, indicating it represents a largely independent biomarker subset.
  • Intratumoral heterogeneity: Marked intratumoral heterogeneity was observed in resected FGFR2b‑positive cases (88%), which has implications for sampling and test interpretation.
  • Survival outcomes: FGFR2b‑positive tumors showed a trend toward worse overall survival, but no statistically significant survival difference was demonstrated after accounting for clinical factors.

Overall, FGFR2b defines a small, distinct subgroup of gastric cancers, more enriched in metastatic/unresectable disease, without clear overlap with other key biomarkers and without a confirmed adverse prognostic impact in this cohort.

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