MMR与PD-L1在Ⅱ期术后结直肠癌中的差异性表达

Differential expression of MMR and PD-L1 protein in stage Ⅱ colorectal cancer

目的探讨错配修复基因(MMR)和细胞程序性死亡配体1(PD-L1)在Ⅱ期结直肠癌(CRC)组织中的一致性及差异性。方法选取2016年1月到2017年10月接受手术治疗的Ⅱ期CRC患者50例,免疫组化法检测术后病理组织标本中4种MMR蛋白:MutL同源蛋白1(MLH1)、Muts同源蛋白2(MSH2)、Muts同源蛋白6(MSH6)、减数分裂后分离蛋白2(PMS2)和PD-L1的表达,并分析二者的相关性。结果结直肠癌组织中MMR缺失(dMMR)率和PD-L1的阳性率分别为32%(16/50)和38%(19/50),dMMR和PD-L1双阳性的患者为20%(10/50);dMMR患者中PD-L1的阳性率高于错配修复功能完整患者,62.5%(10/16)vs 26.5%(9/34),差异具有统计学意义(X^2=5.995,P=0.027),PD-L1的表达与MLH1和MSH2表达缺失有关(P=0.024和0.049);PD-L1阳性患者(n=19)中dMMR与错配修复功能完整的发生率差异无统计学意义,52.6%vs47.4%。结论 PD-L1蛋白与dMMR存在差异性表达,在使用靶向药物治疗前,应综合考虑两种生物标志物的表达情况更精准地筛选患者。

ObjectiveTo investigate the difference and consistency between MMR and PD-L1 in stage Ⅱ colorectal cancer （CRC）. MethodsA total of fifty patients performed operation from January 2016 to October 2017 and diagnosed as stage Ⅱ CRC were enrolled in the study. The expression of MMR （MutL homolog 1 （MLH1）、MutS homolog 2 （MSH2）、MutS homolog 6 （MSH6）、Postmeiotic segregation increased 2 （PMS2） and PD-L1 were detected by immunohistochemistry, and the association between MMR and PD-L1 were analyzed. ResultsThe rate of dMMR and of PD-L1 positive cases was 32% （16/50） and 39% （19/50） in total CRC specimens. 20% （10/50） positive PD-L1 patients had dMMR tumors. The expression of PD-L1 was higher in the dMMR group than in the pMMR group, the difference between the two groups was statistically significant [62.5% （10/16） vs 26.5% （9/34）, χ2=5.995, P=0.027]. The expression of PD-L1 was associated with MLH1 and MSH2 loss （P=0.024 and 0.049）; No different trend between expression rate of dMMR and proficient mismatch repair （52.6%, 10/19 vs 47.4%, 9/19） in positive PD-L1 stage Ⅱ CRC. ConclusionPD-L1 showed the difference expression in dMMR CRC tumor, it was implied that we need to take both dMMR and PD-L1 factors into consideration to screen suitable patients before targeting therapy.