Circulating tumor cells with FGFR2 expression might be useful to identify patients with existing FGFR2-overexpressing tumor

Abstract

Fibroblast growth factor receptor (FGFR) is associated with proliferation, migration, and angiogenesis of carcinomas, and FGFR signaling inhibitors are considered a key drug for the treatment of solid tumors with FGFR overexpression. Amplification of FGFR2 is reportedly identified in 3%-10% of gastric cancers (GCs). The aim of this study is to clarify whether the identification of the circulating tumor cells (CTCs) with FGFR2 overexpression is useful to detect patients with FGFR2-overexpressing GC. One hundred GC patients who underwent gastrectomy were enrolled. A total volume of 8 mL of peripheral blood was collected from each patient just before gastrectomy, and mononuclear cells were enriched by Ficol density gradient centrifugation. These cells were immunostained with PI/CD45/EpCAM/FGFR2. The number of CTCs with FGFR2 expression in each sample was enumerated by FACScan. The FGFR2 expression level of the resected primary tumor was assessed by immunohistochemistry. The number of FGFR2-positive CTCs in the GC patients' peripheral blood was significantly correlated with the FGFR2 expression level of the primary GC. The relapse-free survival of the patients with FGFR2-positive CTCs (≥5 cells/10 mL blood) was significantly poorer (P = .018, log-rank) than that of the patients without FGFR2-positive CTCs (<5 cell/10 mL blood). These findings suggested that the determination of FGFR2-positive CTCs might help identify an existing tumor with FGFR2 overexpression.

Keywords: CTC; FGFR2; clinical study; flow cytometry; gastric cancer.