Molecular Oncology and Therapeutics, Osaka City University Graduate School of Medicine, Osaka, Japan.
Department of Gastroenterological Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan.
Cancer Sci. 2020 Dec;111(12):4500-4509. doi: 10.1111/cas.14654. Epub 2020 Oct 1.
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.
成纤维细胞生长因子受体(FGFR)与癌的增殖、迁移和血管生成有关,FGFR 信号抑制剂被认为是治疗 FGFR 过表达实体瘤的关键药物。据报道,FGFR2 的扩增在 3%-10%的胃癌(GC)中被识别。本研究旨在阐明鉴定过表达 FGFR2 的循环肿瘤细胞(CTC)是否有助于检测 FGFR2 过表达的 GC 患者。我们纳入了 100 名接受胃切除术的 GC 患者。每位患者在胃切除术前采集 8mL 的外周血,通过菲可密度梯度离心法富集单核细胞。这些细胞用 PI/CD45/EpCAM/FGFR2 免疫染色。通过 FACScan 对每个样本中表达 FGFR2 的 CTC 数量进行计数。通过免疫组织化学评估切除的原发性肿瘤中 FGFR2 的表达水平。GC 患者外周血中 FGFR2 阳性 CTC 的数量与原发性 GC 中 FGFR2 的表达水平显著相关。FGFR2 阳性 CTC(≥5 个/10mL 血液)患者的无复发生存率明显较差(P=0.018,log-rank),无 FGFR2 阳性 CTC(<5 个/10mL 血液)患者。这些发现表明,确定 FGFR2 阳性 CTC 可能有助于识别存在 FGFR2 过表达的肿瘤。