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Low positivity rate of fibroblast growth factor receptor 2b is associated with heterogeneous expression in gastric cancer

  • 0Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-Ro 43-Gil, Songpa-Gu, Seoul, 05505, Republic of Korea.
Gastric Cancer : Official Journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association +

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April 11, 2025

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April 11, 2025

View abstract on PubMed

Summary

This summary is machine-generated.

Fibroblast growth factor receptor 2b (FGFR2b) overexpression is heterogeneous in gastric cancer, with a 4.1% positivity rate. Single biopsies may not accurately detect FGFR2b overexpression due to significant intratumoral and intrapatient variability.

Area Of Science

  • Oncology
  • Gastroenterology
  • Molecular Biology

Background

  • Bemarituzumab targets fibroblast growth factor receptor 2b (FGFR2b) and is in phase 3 gastric cancer (GC) trials.
  • Limited data exists on FGFR2b overexpression characteristics, prognostic value, and expression patterns in GC.

Purpose Of The Study

  • Investigate clinicopathologic features of FGFR2b-positive GC.
  • Assess survival outcomes in FGFR2b-positive GC.
  • Evaluate FGFR2b expression concordance across biopsy, surgical, and metastatic specimens.

Main Methods

  • Retrospective study of 466 patients with stages I-IV GC.
  • Analyzed biopsy-surgical (n=163) and primary-metastatic (n=135) specimen pairs.
  • Defined FGFR2b overexpression as moderate-to-strong membranous/cytoplasmic expression in ≥10% of tumor cells; assessed FGFR2 amplification via in situ hybridization.

Main Results

  • FGFR2b overexpression found in 4.1% of GC patients (surgical: 4.1%, biopsy: 1.1%, metastatic: 3.0%).
  • Overexpression correlated with deeper invasion and perineural invasion in resectable GC but did not impact survival.
  • Low concordance observed between biopsy-surgical (0.6%) and primary-metastatic (0.7%) specimens; FGFR2 amplification present in 94.1% of FGFR2b-overexpressing cases.

Conclusions

  • Significant intratumoral and intrapatient heterogeneity in FGFR2b expression was observed.
  • Single endoscopic biopsies may not reliably assess FGFR2b overexpression due to expression variability.
  • The overall 4.1% positivity rate in GC is likely influenced by this substantial expression heterogeneity.

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