错配修复蛋白与CDX-2、p53在结直肠腺癌中的表达及对临床病理特征的影响

Expression of mismatch repair proteins,CDX-2,and p53 in colorectal adenocarcinoma and their association with clinicopathological characteristics

背景微卫星不稳定性(microsatellite instability,MSI)是由DNA错配修复蛋白表达阴性所导致,是结直肠癌发生的重要途径之一.同源异型框转录因子(caudal-related homeobox transcription factor 2,CDX-2)及p53在结直肠癌中均可发挥抑癌作用并与患者的部分临床病理特征相关.目的探讨结直肠腺癌中错配修复蛋白(MLH1、MSH2、PMS2、MSH6)与CDX-2、p53的表达及其临床意义.方法选取2017-01/2021-03扬州大学附属医院收治的结直肠腺癌患者175例,采用免疫组化方法检测错配修复蛋白MLH1、MSH2、PMS2、MSH6及CDX-2、p53在结直肠腺癌中的表达情况,各组中的分布差异采用χ^(2)检验,各指标间的相关性采用Spearman等级相关.结果175例结直肠腺癌患者中四种错配修复蛋白表达阴性者39例(22.3%),其中MSH2、MSH6、MLH1、PMS2的表达阴性者分别为12例(6.9%)、1例(0.6%)、17例(9.7%)、28例(16.0%);其中91例结直肠腺癌中CDX-2表达阴性共34例(35.1%),28例结直肠腺癌中p53表达阴性共7例(25%).错配修复蛋白表达阴性与结直肠腺癌患者发病年龄、肿瘤部位及分化程度有显著性(P<0.05),在患者性别、肿瘤浸润深度及淋巴结转移方面差异均无显著性.错配修复蛋白与CDX-2、p53表达水平均无相关性.结论错配修复蛋白的表达与结直肠癌发病年龄、肿瘤部位及分化程度有关.检测错配修复蛋白对于结直肠腺癌的早期诊断、制定治疗方案及评估预后具有重要的临床意义.

BACKGROUND Microsatellite instability is caused by loss of expression of DNA mismatch repair(MMR)proteins,which are involved in one of significant pathways that lead to colorectal cancer development and progression.Both Cdx-2 and p53 play an inhibitory role in colorectal cancer and are related to some clinicopathological features.AIM To analyze the significance of expression of MMR proteins(MLH1,MSH2,PMS2,and MSH6),CDX-2,and p53 in colorectal adenocarcinoma.METHODS A total of 175 patients with colorectal adenocarcinoma who were operated at the Affiliated Hospital of Yangzhou University from January 2017 to March 2021 were selected.The expression levels of MLH1,MSH2,PMS2,MSH6,CDX-2,and p53 in colorectal cancer were detected by immunohistochemical method.The association of the expression of the above proteins with clinicopathological features of colorectal adenocarcinoma was explored by chi-square test,and Spearman rank correlation was used for correlation analysis.RESULTS Among 175 colorectal adenocarcinoma patients,there were 39 patients with negative expression of all four MMR proteins(22.3%).The negative expression of MSH2,MSH6,MLH1,and PMS2 was found in 12(6.9%),1(0.6%),17(9.7%),and 28(16.0%)cases,respectively.Among 91 colorectal adenocarcinoma patients,34(35.1%)had negative expression of CDX-2,and 7(25%)had negative expression of p53 in colorectal adenocarcinoma.The negative expression of MMR proteins was significantly correlated with the age of onset,tumor site,and degree of differentiation in colorectal adenocarcinoma patients(P<0.05),but had no significant correlation with patient gender,tumor invasion depth,or lymph node metastasis(P>0.05).There was no correlation between the expression of MMRs protein and that of CDX-2 and p53(P>0.05).CONCLUSION The expression of MMR proteins is related to the age of onset,tumor site,and degree of differentiation.The detection of MMR proteins has important clinical significance for the early diagnosis of colorectal adenocarcinoma,the formulation of therapeutic plan,and the assessment of prognosis.