Kim Hyunjin, Park Sujin, Kang So Young, Ahn Soomin, Kim Kyoung-Mee
Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea.
Pathology Center, Seegene Medical Foundation, Seoul 06351, Korea.
Diagnostics (Basel). 2022 Sep 28;12(10):2355. doi: 10.3390/diagnostics12102355.
Fibroblast growth factor receptor-2 (FGFR2) gene alterations have been identified in solid tumors. FGFR2 amplification is found in 2−9% of gastric carcinomas. We hypothesized that FGFR2 could be associated with peritoneal seeding and studied 360 advanced gastric carcinoma patients; 222 (61.7%) were male, 246 (73.7%) had poorly differentiated histology, and 175 (48.6%) presented with peritoneal seeding. High tumor mutation burden (TMB) was observed in 44 (12.2%) patients, high microsatellite instability (MSI) was observed in 12 (3.33%) patients, ERBB2 amplification was observed in 44 (12.2%) patients, EBV positivity was observed in 10 (10/278; 3.6%) patients, and PD-L1 positivity was observed in 186 (186/264; 70.5%) cases. We found FGFR2 amplification in 26 (7.2%) patients, of which 12 (46.2%) were female and 22 (84.6%) had poorly differentiated histology. In these 26 cases, the copy number of FGFR2 amplification ranged from 3.7 to 274. Eighteen of them showed seeding, and this association was statistically significant (18/26, 69.2%; 157/334, 47%; p = 0.023). In addition, high TMB was significantly associated with seeding (p = 0.028; OR = 1.83). Poorly differentiated histology was significantly associated with seeding (p = 0.04) but not with FGFR2 amplification (p > 0.1). Seeding was frequent in gastric carcinoma patients with FGFR2 amplification, in patients with high TMB, or in those who were female. The subgroup of patients with FGFR2 amplification could be potential candidates for targeted therapeutic agents.
在实体瘤中已发现成纤维细胞生长因子受体2(FGFR2)基因改变。在2%至9%的胃癌中发现FGFR2扩增。我们推测FGFR2可能与腹膜种植有关,并对360例晚期胃癌患者进行了研究;其中222例(61.7%)为男性,246例(73.7%)组织学分化差,175例(48.6%)出现腹膜种植。44例(12.2%)患者观察到高肿瘤突变负荷(TMB),12例(3.33%)患者观察到高微卫星不稳定性(MSI),44例(12.2%)患者观察到ERBB2扩增,10例(10/278;3.6%)患者观察到EBV阳性,186例(186/264;70.5%)病例观察到PD-L1阳性。我们在26例(7.2%)患者中发现FGFR2扩增,其中12例(46.2%)为女性,22例(84.6%)组织学分化差。在这26例病例中,FGFR2扩增的拷贝数范围为3.7至274。其中18例出现种植,这种关联具有统计学意义(18/26,69.2%;157/334,47%;p = 0.023)。此外,高TMB与种植显著相关(p = 0.028;OR = 1.83)。组织学分化差与种植显著相关(p = 0.04),但与FGFR2扩增无关(p > 0.1)。FGFR2扩增的胃癌患者、高TMB患者或女性患者中种植较为常见。FGFR2扩增患者亚组可能是靶向治疗药物的潜在候选者。