Correlation and Overlap Between Claudin 18.2 and FGFR2b Overexpression: A Tissue Microarray Study With 1,538 Gastric Carcinomas.

Purpose: Claudin 18.2 (CLDN18.2) and fibroblast growth factor receptor 2b (FGFR2b) have recently emerged as promising therapeutic targets for advanced gastric cancer (GC). Before integrating CLDN18.2 and FGFR2b into routine practice, for optimal treatment planning, it is important to consider whether there exists an overlap between these biomarkers.

Materials and methods: We evaluated CLDN18.2 expression in many patients with GC (n=1,538) using tissue microarrays that had been previously used to evaluate FGFR2b overexpression. We investigated the overlap between CLDN18.2 and FGFR2b expression and evaluated the clinicopathological features and prognostic implications of CLDN18.2 expression.

Results: The CLDN18.2 positivity rates at 50% and 75% cutoffs were 34.7% and 24.4%, respectively. Heterogeneous expression was identified in 335 (23.5%) of 1426 cases with multiple tissue microarray cores. FGFR2b positivity at >0% cutoff was identified in 47 (3.1%) patients with more marked intratumoral heterogeneity than that observed with CLDN18.2. CLDN18.2 positivity (59.6%) in FGFR2b-positive GCs was significantly higher than that (33.9%) in FGFR2b-negative GCs (P<0.001). Concurrent FGFR2b- and CLDN18.2-positive GCs accounted for 1.8% of all patients, and FGFR2b-positive tumor cells were also positive for CLDN18.2 in approximately 75% of these cases. CLDN18.2 positivity was associated with poorly differentiated histology (P<0.001) and advanced pT and pN stages (P<0.03), but not with overall survival.

Conclusions: CLDN18.2 and FGFR2b were significantly associated with each other, suggesting a considerable overlap. This finding may have important clinical implications on the optimal treatment strategy for CLDN18.2-positive GC.