Abstract
Abstract [Background] Amplification of the fibroblast growth factor receptor 2 (FGFR2) is reportedly identified in 3-10% of primary gastric cancers (GCs). We found that FGFR2 overexpression was closely associated with poor prognosis of patients with gastric cancer. Recently, FGFR signaling inhibitors have been considered a key drug in the treatment of GCs with FGFR2 overexpression. FGFR2 overexpression can be assessed by immunohistochemical staining of primary tumors; however, this method does not sufficiently reflect FGFR2 expression in recurrent tumors owing to the heterogeneity of tumor cells between primary and recurrent tumors. Circulating tumor cells (CTCs) might overcome this issue of “temporal” and “spatial” heterogeneity. This study aimed to assess the significance of the detection of FGFR2-positive CTCs in patients with gastric cancer. [Methods] Seventy-eight patients with gastric cancer who underwent gastrectomy in our hospital were enrolled in this study. A total volume of 10 ml of peripheral blood was collected prior to surgery from each patient, and mononuclear cells were enriched by Ficol density gradient centrifugation. These cells were immunostained with PI/CD45/EpCAM/FGFR2 and PI/CD45/EpCAM/CK. The number of cells in each sample was enumerated depending on the positivity of EpCAM, FGFR2, and CK by fluorescence-activated cell sorting (FACS). FGFR2 expression was assessed by immunohistochemical staining of resected specimens. Patients were categorized into four groups as follows: group IHC-0 (n=32), no staining; group IHC-1+ (n=24), cytoplasmic staining in 1-19% or membranous staining in 1-5%; group IHC-2+ (n=16), cytoplasmic staining in 80-100% or membranous staining in 5-19%; group IHC-3+ (n=6), membranous staining in 20-100%. [Results] FGFR2+ cells were detected in 43 (55%) of 78 cases. Among these cases, CK+ cells or EpCAM+ cells were detected in 35 (81%) of 43 cases. By group, the proportions of FGFR2+ cells were 44% in group IHC-0, 52% in group IHC-1+, 69% in group IHC-2+, and 100% in group IHC-3+. The mean number of FGFR2+ cells from patient samples in the IHC-0, IHC-1+, IHC-2+, and IHC-3+ groups were 12, 11, 16, and 54 (per 10 ml peripheral blood), respectively, with a significant difference between group IHC-0 and group IHC-3+, group IHC-1+ and group IHC-3+, and group IHC-0 and group IHC-2+ (p=0.001, p=0.008 and p=0.034, respectively, by Mann-Whitney U test). Among 68 patients with R0 and pStage I-III, the recurrence-free survival of patients with an FGFR2+ cell count ≧10 cells / 10 ml was significantly poorer than that of patients with an FGFR2+ cell count <10 cells / 10 ml (p = 0.018, by logrank test). [Conclusion] Detection of CTCs with FGFR2 expression by FACScan might be a useful approach to identify gastric cancer patients who would benefit the most from FGFR inhibitor treatment. Citation Format: Kenji Kuroda. Significance of circulating tumor cells (CTCs) with fibroblast growth factor 2 expression in gastric cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1366.
Published Version
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