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

Haruki Ogawa ^1,2, Hiroyuki Abe ¹, Koichi Yagi ²

⁰Department of Pathology, Graduate School of Medicine, the University of Tokyo, 7-3-1 Hongo, Bunkyo-Ku, 113-0033, Tokyo, Japan.

Virchows Archiv : an International Journal of Pathology +

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August 30, 2025

View abstract on PubMed

Summary

Fibroblast growth factor receptor 2b (FGFR2b) expression is inconsistent between primary gastric tumors and peritoneal dissemination (PD). Testing both tumor types may identify patients for targeted therapy.

Area Of Science

Oncology
Gastroenterology
Molecular Biology

Background

Gastric cancer with peritoneal dissemination (PD) has a poor prognosis and limited treatment options.
Fibroblast growth factor receptor 2b (FGFR2b)-targeted therapy is a potential treatment for FGFR2b-positive tumors.
The expression and amplification of FGFR2b in PD are not well understood.

Purpose Of The Study

To investigate FGFR2b expression and gene amplification in matched primary gastric tumors and PD tissues.
To assess the association of FGFR2b status with HER2, CLDN18, and PD-L1.

Main Methods

Immunohistochemistry (IHC) for FGFR2b on 84 matched primary and PD tissues.
FGFR2 fluorescence in situ hybridization (FISH) on IHC-positive samples.

Main Results

FGFR2b expression was detected in 7.1% of primary tumors and 4.8% of PD samples.
Expression was heterogeneous and discordant between primary and PD tissues in most cases.
FGFR2 amplification occurred in 6 of 10 IHC-positive samples.
No significant correlation was found between FGFR2b status and HER2, CLDN18, or PD-L1.

Conclusions

FGFR2b expression in gastric cancer is spatially heterogeneous and discordant between primary tumors and PD.
Testing both primary tumor and PD tissue may be necessary to identify candidates for FGFR2b-targeted therapy.
FGFR2b is a potential therapeutic target for a subset of PD-positive gastric cancers lacking other biomarker expression.

Keywords:

Biomarker testing FGFR2b Gastric cancer Molecular targeted therapy Peritoneal dissemination