HER2阳性胃癌组织MSI和PD-L1表达及意义

EXPRESSION AND SIGNIFICANCE OF MICROSATELLITE INSTABILITY AND PROGRAMMED DEATH-LIGAND 1 IN HER2-POSITIVE GASTRIC CANCER

目的验证二代测序(NGS)与免疫组织化学(IHC)技术在胃癌人表皮生长因子受体2(HER2)状态评估中的一致性,分析HER2阳性胃癌微卫星不稳定性(MSI)、程序性死亡配体1(PD-L1)表达与临床病理特征的关系。方法收集行胃癌手术且术后组织标本IHC检测HER2(3+)病人92例。采用NGS技术检测病人癌组织中HER2基因扩增情况及MSI状态;采用PD-L1 IHC 22C3 pharmDx试剂盒检测癌组织中PD-L1的表达情况,结果分别以阳性组合评分(CPS)和肿瘤比例评分(TPS)进行计算。结果IHC检测HER2阳性的胃癌病人92例,NGS检测84例存在HER2基因扩增,IHC与NGS检测结果的一致率为91.3%。92例HER2阳性胃癌病人中,微卫星稳定(MSS)病人90例(97.8%),微卫星高度不稳定(MSI-H)病人2例(2.2%);84例存在HER2基因扩增的病人均呈MSS状态,无MSI-H病人。按CPS标准,92例HER2阳性病人PD-L1阳性率为89%,PD-L1表达与临床病理特征之间无相关性。按TPS标准,92例HER2阳性病人PD-L1阳性率为24%,PD-L1表达与临床病理特征之间无相关性。结论IHC和NGS技术检测胃癌组织HER2表达的一致率较高。胃癌组织中HER2基因扩增与MSI-H可能存在互斥关系。HER2阳性胃癌CPS标准下的PD-L1阳性率高于TPS标准下的PD-L1阳性率,但二者均与临床病理特征无关。

Objective To verify the consistency of next-generation sequencing(NGS)and immunohistochemistry(IHC)in assessing the status of human epidermal growth factor receptor 2(HER2)in gastric cancer,and to investigate the association of microsatellite instability(MSI)and programmed death ligand 1(PD-L1)expression with clinicopathological characteristics of HER2-positive gastric cancer.Methods A total of 92 patients who underwent gastric cancer surgery and whose postoperative tissue specimen was HER2(3+)based on IHC were enrolled.NGS technique was used to detect HER2 gene amplification and MSI status in cancer tissue;PD-L1 IHC 22C3 pharmDx kit was used to measure the expression of PD-L1 in cancer tissue;the Results were calculated by combined positive score(CPS)and tumor proportion score(TPS).Results In this study,there were 92 gastric cancer patients with positive HER2.NGS detection showed that 84 patients had HER2 gene amplification,and the consistency rate between IHC and NGS detection was 91.3%.Among the 92 patients with HER2-positive gastric cancer,90(97.8%)had microsatellite stable(MSS)tumors and 2(2.2%)had microsatellite instability-high(MSI-H)tumors;and 84 patients with HER2 gene amplification had MSS tumors,while no patient had MSI-H tumors.According to the CPS criteria,92 HER2-positive patients had a positive rate of PD-L1 of 89%,and there was no association between PD-L1 expression and clinicopathological characteristics.According to the TPS criteria,92 HER2-positive patients had a positive rate of PD-L1 of 24%,and there was no association between PD-L1 expression and clinicopathological characteristics.Conclusion IHC and NGS have a high consistency rate in detecting the expression of HER2 in gastric tissue.There may be a mutually exclusive relationship between HER2 gene amplification and MSI-H in gastric cancer tissue.The positive rate of PD-L1 in HER2-positive gastric cancer under the CPS criteria is higher than that under the TPS criteria,but they are not associated with clinicopathological characteristics.