微卫星不稳定型胃癌及微卫星稳定型胃癌的免疫分型及预后分析
The immune type and prognosis analysis in microsatellite instability and stability gastric cancer

摘要：目的 探讨CD8、CD68、PD-1及PD-L1在微卫星稳定型(MSS)/不稳定型(MSI)胃癌中的表达水平及微卫星状态对胃癌的预后影响。方法 收集空军军医大学第一附属医院消化病医院2012年3月至2012年8月连续的胃癌病例，记录其临床病理学资料及随访结果。采用免疫组织化学染色法检测60例胃癌石蜡切片中错配修复分子MLH1、MSH2、MSH6、PMS2，CD8、CD68、PD-1、PD-L1表达水平。采用Log-rank法分析不同组间的生存预后。结果 60例胃癌中MSI胃癌病例15例(25.0%)。MSS胃癌及MSI胃癌中CD8、PD-1及PD-L1表达无统计学差异，CD68在MSS胃癌中表达高于MSI胃癌(P=0.046)。MSI胃癌以Ⅱ型免疫分型(CD8-PD-L1-)为主，占46.67%，MSS胃癌以Ⅱ型和Ⅳ型(CD8+PD-L1-)为主，占33.33%和31.11%。MSI胃癌5年疾病无进展(P=0.036)及总体生存预后？？(P=0.041)？？优于MSS胃癌。结论 MSI胃癌组织微环境存在钝性免疫反应，但生存预后较好。
ABSTRACT: Objective To investigate the expressions of CD8, CD68, PD-1 and PD-L1 in microsatellite stability/instability (MSS/MSI) gastric cancer and the prognostic value of microsatellite stability. Methods Sixty consecutive primary gastric cancer samples were collected from March 2012 to August 2012. The clinical pathological and survival information was collected as well. Immunohistochemistry of MLH1, MSH2, MSH6, PMS2, CD8, CD68, PD-1 and PD-L1 was conducted for each sample. The survival prognosis was analyzed by log-rank test. Results There were 15 MSI gastric cancer samples (25.0%) with negative staining of MLH1, MSH2, MSH6 and PMS2. There was no significant difference in the expression of CD8, PD-1 or PD-L1 between MSS and MSI gastric cancer, but the CD68 positive macrophages infiltration was higher in MSS than in MSI gastric cancer (P=0.046). Type Ⅱ (CD8-PD-L1-) was the major immune type (46.67%) in MSI gastric cancer, and the main immune type of MSS gastric cancer was type Ⅱ(33.33%) and type Ⅳ (CD8+PD-L1-, 31.11%). The disease-free survival (P=0.036) and overall survival (P=0.041) in MSI gastric cancer was longer than in MSS. Conclusion MSI gastric cancer predicts a better prognosis although the tumor microenvironment shows a lower immune response