错配修复蛋白和p53蛋白表达与结直肠癌的临床病理关系及其相关性

Correlation of the expression of mismatch repair protein and p53 protein with clinicopathological features in colorectal cancer

目的探讨错配修复蛋白(mismatch repair protein,MMRP)及p53蛋白在结直肠癌(colorectal cancer,CRC)中的表达,进而分析微卫星不稳定(microsatellite instability,MSI)、p53与CRC临床病理特征的关系及其相关性。方法采用组织芯片及免疫组化法对980例CRC中4种MMRP及p53进行检测,将4种MMMP中的1种及以上表达缺失定为MSI组,全部阳性表达定为微卫星稳定(microsatellite stable,MSS)组。结果 (1)MMRP表达缺失率为11%,MLH1、PMS2、MSH2及MSH6的表达缺失率分别为7.3%、7.1%、2.0%及1.9%;其中共同缺失表达类型为MLH1-PMS2、MSH2-MSH6者分别为52例、14例,统计分析结果显示二者均呈正相关(rs=0.712),4种蛋白均缺失者3例。(2)p53阳性率为59.1%。(3)MSI与患者年龄、肿瘤部位、大小、组织学类型、淋巴结转移、临床分期及Ki-67有关(P<0.05)。(4)p53与组织学类型、大体分型、浸润深度、远处转移及Ki-67有关(P<0.05)。(5)MSI与p53呈负相关(rs=-0.118)。结论 MLH1、PMS2缺失表达较MSH2和MSH6多见。MLH1与PMS2、MSH2与MSH6常常协同表达或缺失。MSI及p53与CRC临床病理特征关系密切,对预测CRC的风险、恶性程度的评估等具有指导意义。MSI与p53表达呈负相关,提示二者可能参与CRC的不同发生、发展过程。

Purpose To investigate the expression of mismatch repair protein （MMRP） and p53 protein in colorectal cancer （CRC）, and then to analyze their relationship with clinicopathologic features and its correlation. Methods Tissue microarray and auto-immu- nohistochemical staining were used to detect the expression of four mismatch repair proteins and p53 protein in paraffin embedded tissue samples from 980 CRC patients. Loss expression of any MMRP was labeled as the microsatellite instability （MSI） , and all positive expression was labeled as the microsatellite stable （MSS） group. Results Defects in MMRP was found in I 1% cases analyzed. The rate of loss expression in MLH1, PMS2, MSH2 and MSH6 was 7.3% , 7. 1% , 2.0% and 1.9% , respectively. Among them, double protein absence was found in MLH1/PMS2 in 52 cases and MSH2/MSH6 14 cases, the expression of MLH1 and PMS2, MSH2 and MSH6 showed positive correlation （ rs = 0. 712, P 〈 0. 001 ）. Loss of all the four MMRP was only detected in three cases. The positive expression rate of p53 was 59. 1%. MSI was associated with age, tumor location, tumor size, histological type, lymph node metastasis, clinical stage, Ki-67 （ P 〈 0. 05 ） , but had no relationship with gender, gross type, differentiation degree, infiltration depth, vascular invasion, nerve recidivism, distant metastasis and CEA levels （P 〉 0. 05 ）. The expression of p53 was correlated to histological type, gross type, infiltration depth, distant metastasis and Ki-67 （ P 〈 0. 05 ）, but not to age, gender, tumor location, tumor size, differentiation degree, clinical stage, lymph node metastasis, vascular invasion, nerve recidivism, and CEA levels （ P 〉 0. 05 ）. MSI was negatively correlated with p53 （r = -0. 118）. Conclusion The loss expression of MLH1 and PMS2 is more common than MSH2 and MSH6. MLH1 and PMS2, MSH2 and MSH6 are often expressed or deleted together. MSI and p53 have a close relationship with the clinieopathological features in eolorectal cancer, and therefore may be biological indicators for predicting the risk and estimating malignant degree of CRC. MSI is negatively correlated with p53, which indicates that both may participate in different stage of the pathogenesis of eoloreetal cancer.