Objective: To investigate the relationship of PD-L1 protein expression and gene amplification in gastric cancer and their correlation with clinicopathologic factors. Methods: The cohort included 247 gastric cancer specimens with follow-up data and clinicopathologic data obtained from Shanxi Cancer Hospital in 2011. PD-L1 expression was detected by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). Results: PD-L1 protein was expressed in 25.9% (64/247) of the tumor cells and 26.7% (66/247) of the tumor infiltrating immune cells (IC). There was a correlation between the two (P<0.01). The expression of PD-L1 in tumor cells correlated with the degree of differentiation and tumor diameter(P<0.05). The PD-L1 expression in IC correlated with vascular tumor thrombi(P<0.05). The amplification rate of PD-L1 gene detected by FISH was 19.0% (47/247), and was associated with age, large/small curvature of the stomach, tumor location, tumor diameter, and lymph node metastasis(P<0.05). The positive coincidence rate of the two methods was 25.0% (16/64), negative coincidence rate was 83.0% (152/183), and total coincidence rate was 68.0% (168/247), suggesting that the coincidence of IHC and FISH was poor (P=0.157). There was a negative correlation between PD-L1 protein expression on tumor cells and prognosis in gastric cancer. There was no significant correlation between PD-L1 protein expression on IC and PD-L1 gene amplification with prognosis. Vascular tumor thrombi, tumor diameter, depth of invasion, and lymph node metastasis were all poor prognostic factors of gastric cancer(P<0.05). Multivariate Cox regression analysis showed that PD-L1 protein expression, depth of invasion and lymph node metastasis were all independent prognostic risk factors for gastric cancer. Conclusions: Concordance between PD-L1 protein expression and gene amplification is poor. PD-L1 protein expression may signify poor prognosis. There is no significant correlation between PD-L1 gene amplification and prognosis of patients with gastric cancer.
目的： 探讨胃癌中程序性死亡分子配体1(PD-L1)蛋白表达和基因扩增的相关性及与临床病理特征的相关关系。 方法： 选取山西省肿瘤医院2011年有完整随访资料和临床病理资料的胃癌患者247例，应用免疫组织化学(IHC)标记及荧光原位杂交(FISH)技术检测胃癌组织中PD-L1蛋白表达和基因扩增情况。 结果： (1)PD-L1蛋白表达与胃癌临床病理特征的关系：在胃癌组织，肿瘤细胞中PD-L1蛋白表达阳性率为25.9%(64/247)，肿瘤浸润免疫细胞(IC)中PD-L1蛋白表达阳性率为26.7%(66/247)，两者表达具有相关性(P<0.01)，肿瘤细胞中PD-L1表达与分化程度和肿瘤直径有相关性(P<0.05)，免疫细胞中PD-L1表达与有无脉管癌栓有相关性(P<0.05)。(2)PD-L1基因扩增与胃癌临床病理特征的关系：FISH检测PD-L1基因扩增率为19.0%(47/247)。PD-L1基因扩增与年龄、胃大/小弯、肿瘤部位、肿瘤直径及淋巴结转移有相关性(P<0.05)。(3)IHC检测的肿瘤细胞中PD-L1蛋白表达与FISH检测的PD-L1基因扩增，两种检测方法阳性符合率为25.0%(16/64)，阴性符合率为83.0%(152/183)，总符合率为68.0%(168/247)，IHC和FISH检测结果一致性较差(P＝0.157)。(4)单因素生存分析：肿瘤细胞中PD-L1蛋白表达与预后呈负相关关系，免疫细胞中PD-L1蛋白表达和PD-L1基因扩增与预后均没有明显相关性。脉管癌栓、肿瘤直径、浸润深度和淋巴结转移均是胃癌的不良预后因素(P<0.05)。(5)多因素Cox回归分析：肿瘤细胞中PD-L1蛋白表达、浸润深度和淋巴结转移均为影响胃癌预后的独立危险因素(P<0.05)。 结论： 胃癌中PD-L1蛋白表达与基因扩增一致性较差；PD-L1蛋白表达提示预后较差；PD-L1基因扩增与预后无明显相关性。.
Keywords: Gene amplification; Prognosis; Programmed death-ligand 1(PD-L1); Stomach neoplasms.