Lee Heonwoo, Ryu Min-Hee, Lee In-Seob, Ahn Ji Yong, Lee Jeong Hoon, Lee Hyungeun, Kim Hyung-Don, Park Young Soo
Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-Ro 43-Gil, Songpa-Gu, Seoul, 05505, Republic of Korea.
Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-Ro 43-Gil, Songpa-Gu, Seoul, 05505, Republic of Korea.
Gastric Cancer. 2025 Apr 11. doi: 10.1007/s10120-025-01611-z.
Bemarituzumab, a monoclonal antibody targeting fibroblast growth factor receptor 2b (FGFR2b), is under evaluation in phase 3 trials of gastric cancer (GC) trials. However, data on the characteristics, prognostic significance, and heterogenous expression patterns of FGFR2b overexpression in GC remain limited. Therefore, this study aims to investigate the clinicopathologic characteristics and survival outcomes of FGFR2b-positive GC, along with the expression concordance across biopsy, surgical, and metastatic specimens.
This retrospective study included 466 patients with stages I-IV GC. Biopsy-surgical and primary-metastatic specimen pairs were available for 163 and 135 patients, respectively. FGFR2b overexpression was defined as moderate-to-strong membranous and/or cytoplasmic expression in ≥ 10% of tumor cells. FGFR2 amplification was evaluated using chromogenic in situ hybridization.
FGFR2b overexpression was observed in 4.1% of patients, with 14/341 surgical specimens (4.1%), 3/284 gastric biopsies (1.1%), and 4/135 metastatic specimens (3.0%). FGFR2b overexpression correlated with deeper invasion and perineural invasion in resectable GC. However, it did not influence survival outcomes in resectable or metastatic GC. Among 163 biopsy-surgical pairs, FGFR2b overexpression was observed in only one pair (0.6%). Similarly, among 135 paired primary-metastatic specimens, FGFR2b overexpression was observed in one (0.7%). FGFR2 gene amplification occurred in 16/17 (94.1%) cases with FGFR2b overexpression.
Significant intratumoral and intrapatient heterogeneity is observed in FGFR2b overexpression. Given this variability in expression levels, a single endoscopic biopsy may not accurately assess FGFR2b overexpression. The FGFR2b positivity rate in gastric cancers was 4.1%, likely due to the substantial heterogeneity in its expression.
贝玛妥珠单抗是一种靶向成纤维细胞生长因子受体2b（FGFR2b）的单克隆抗体，正在胃癌（GC）的3期试验中进行评估。然而，关于GC中FGFR2b过表达的特征、预后意义和异质性表达模式的数据仍然有限。因此，本研究旨在探讨FGFR2b阳性GC的临床病理特征和生存结果，以及活检、手术和转移标本中的表达一致性。
这项回顾性研究纳入了466例I-IV期GC患者。分别有163例和135例患者可获得活检-手术标本对和原发-转移标本对。FGFR2b过表达定义为≥10%的肿瘤细胞中存在中度至强的膜性和/或细胞质表达。使用显色原位杂交评估FGFR2扩增情况。
4.1%的患者观察到FGFR2b过表达，其中14/（341例）手术标本（4.1%）、3/（284例）胃活检标本（1.1%）和4/（135例）转移标本（3.0%）。FGFR2b过表达与可切除GC的更深浸润和神经周围浸润相关。然而，它并未影响可切除或转移性GC的生存结果。在163对活检-手术标本中，仅1对（0.6%）观察到FGFR2b过表达。同样，在135对原发-转移标本中，1对（0.7%）观察到FGFR2b过表达。16/（17例）（94.1%）FGFR2b过表达的病例发生了FGFR2基因扩增。
在FGFR2b过表达中观察到显著的肿瘤内和患者内异质性。鉴于表达水平的这种变异性，单次内镜活检可能无法准确评估FGFR2b过表达。胃癌中FGFR2b阳性率为4.1%，可能是由于其表达存在大量异质性。
