摘要目的:探讨高度微卫星不稳定（microsatellite instability-high，MSI-H）胃癌的组织学特征及其PD-L1表达对预后的预测价值。方法:收集2014年3月至2018年12月北京大学肿瘤医院行根治性胃癌手术切除和进行4种主要错配修复蛋白（MLH1、PMS2、MSH2、MSH6）免疫组织化学染色的2 472例患者的临床病理资料。对171例表现为错配修复缺陷（mismatch repair-deficient，dMMR）的患者采用聚合酶链反应（PCR）进行微卫星不稳定性检测。以PCR检测结果为标准，对MSI-H胃癌采用免疫组织化学方法进行PD-L1染色。结果:MSI-H胃癌与老年、女性、胃窦、肠型、肿瘤大于5 cm、缺乏淋巴结转移及PD-L1表达阳性有关（均 P<0.05）。PD-L1表达水平联合阳性评分可作为独立的预后危险因素（ P=0.026， HR=8.385，95% CI=1.293~54.367）。虽然未观察到PD-L1表达模式与预后的关系，但PD-L1表达模式“弥漫”与脉管癌栓侵犯（ P=0.007）、浸润深度（ P=0.040）有关，并且MSI-H+PD-L1阳性胃癌中所有发生复发或死亡的患者，PD-L1表达模式均为“弥漫”。此外，胃癌原发灶和淋巴结转移灶的PD-L1表达水平和表达模式有高度的一致性（ P=0.450）。 结论:MSI-H胃癌具有独特的组织学特征。PD-L1表达水平联合阳性评分为MSI-H胃癌患者一个重要的预后预测指标。PD-L1表达模式“弥漫”或为一个预后预测指标。晚期胃癌患者可以通过转移灶活检来获取其PD-L1表达的水平和模式。

abstractsObjective:To study the clinicopathological features and PD-L1 expression of microsatellite instability-high (MSI-H) gastric cancer.Methods:The clinicopathological data of the 2 472 patients who had undergone radical surgical resection and been performed immunohistochemical staining of four major mismatch repair (MMR) proteins (MLH1, PMS2, MSH2 and MSH6) from March 2014 to December 2018 at Peking University Cancer Hospital were collected. One hundred and seventy-one patients showed mismatch repair-deficient (dMMR), and microsatellite instability of these patients were detected with polymerase chain reaction (PCR). Then, taken PCR results as the standard, PD-L1 was assessed using immunohistochemistry (IHC) in the MSI-H gastric cancers.Results:MSI-H (vs. MSI-L) in gastric cancers was associated with female gender, advanced age, gastric-antrum location, intestinal type, lesion diameter exceeding 5 cm, absence of lymph node metastasis and positive PD-L1 expression ( P<0.05, respectively). Combined positive score (CPS) was an independent risk factor ( P=0.026, HR=8.385, 95% CI=1.293-54.367). Although no relationship between PD-L1 expression pattern and prognosis was observed,"diffuse-pattern" of the PD-L1 expression was related to lymphatic-vascular invasion ( P=0.007) and infiltration depth ( P=0.04). Among the patients with MSI-H and PD-L1 positive gastric cancer, the patients who experienced recurrence or died all had the pattern of "diffuse" PD-L1 expression. Also, regarding the expression level and staining pattern of PD-L1, the metastasis lesion of lymph node had a high coincidence with primary site ( P=0.45). Conclusions:MSI-H gastric cancer shows distinctive clinicopathological characteristics. The CPS can be used as a prognostic indicator in MSI-H gastric cancers, while the "diffuse-pattern" of PD-L1 expression could possibly be used as a prognostic indicator. The patients with advanced gastric cancer could obtain the expression level and staining pattern of PD-L1 using the biopsy material of metastatic lesions.