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.

Recent progress of nanostructure-based enrichment of circulating tumor cells and downstream analysis

“…Kenji Kuroda et al enriched CTCs by density gradient centrifugation and studied the blood samples of 100 patients with gastric cancer before gastrectomy. 159 Immunohistochemical evaluation showed that the number of FGFR2-positive CTCs in peripheral blood was significantly correlated with the expression of FGFR2 in primary gastric cancer. The relapse-free survival rate of FGFR2-positive CTCs This journal is © The Royal Society of Chemistry 2023 patients (≥5 cells/10 mL blood) was significantly lower than that of non-FGFR2-positive CTCs patients.…”

Clinical Developments and Challenges in Treating FGFR2-Driven Gastric Cancer

“…One possible strategy for more successfully predicting the response to FGFR2 inhibitors could be the use of circulating tumour DNA (ctDNA) technology [96]. For instance, the Japanese GI-SCREEN and GOZILA molecular profiling studies revealed that FGFR2 amplification in patients with advanced GC was more frequently detected by ctDNA sequencing (7.7% of cases) compared to by tissue analysis alone (2.6-4.4% of cases), and notably 2 patients with FGFR2 amplification detected by ctDNA sequencing after tumour progression but not by tissue analysis of the pre-treatment sample had responses to FGFR inhibitors [97].…”

Circulating tumour cells in gastrointestinal cancers: food for thought?

“…CTC potentially used as an early diagnostic marker (85.3% sensitivity and 90.3% specificity) [ 27 ] 162 CellSearch Dynamic changes in CTC count (≥2 cells/7.5 ml blood threshold) between baseline and at day 28 after treatment were significantly associated with PFS and OS (NCT01443065) [ 28 ] 93 CellSearch Pre and postoperative CTC levels are prognostic markers for recurrence of advanced gastric cancer after resection [ 123 ] 228 Flow cytometry, immunofluorescent double staining CK + CD44 + cells were significantly more common among patients with distant metastases and were associated with significantly shortened survival [ 30 ] 100 Ficoll FGFR2 + CTCs (≥5 cells/10 ml blood) were associated with poorer RFS. CTCs might be helpful to identify an existing tumour with FGFR2 overexpression [ 31 ] 70 Immunofluorescence CSV + PD-L1 + CTCs are significantly correlated with short survival duration and poor therapeutic response [ 32 ] 150 Ficoll EpCAM − CEA + cells count was significantly associated with 3-year RFS [ 33 ] Hepatocellular carcinoma 62 Multiplex fluorescence in situ hybridisation Mesenchymal-like CTCs (≥1 cells/5 ml blood threshold) are correlated with the risk of early recurrence [ 124 ] 85 Flow cytometry Preoperative GPC3 + CTCs (≥5 cells/8 ml blood threshold) are associated with poor prognosis and are a risk factor for microscopic portal vein invasion (UMIN000025989) [ 125 ] 105 Tapered slit filter Postoperative CTCs were detected in 23.8% of HCC patients and associated with lower survival and higher recurrence in early HCC [ 35 ] 256 Canpatrol CTC count and EMT status were not associated with p...…”

“…Efforts are made to increase the variety of CTC markers to further improve their characterisation [29]. For example, CD44, cytokeratin, fibroblast growth factor, cell surface vimentin protein, programmed cell death ligand-1, carcinoembryonic antigen, and HER2-positive CTCs were used as potential prognostic markers in GC [30][31][32][33][34].…”