[Correlation between mismatch-repair protein expression and clinicopathologic features in 658 colorectal cancers].

Objective: To investigate the expression of mismatch repair (MMR) proteins (MLH1, MSH2, MSH6 and PMS2) in colorectal cancers and to explore the relationship between MMR expression and clinicopathologic features. Methods: Six hundred and fifty-eight colon cancers were collected from January 2016 to January 2017 at Shengjing Hospital of China Medical University. Of the 658 patients there were 409 male and 249 female. The patients were 20 to 92 years old, with average age of (63±5) years old. Expression of MLH1, MSH2, MSH6 and PMS2 protein was detected by immunohistochemical method. Immunohistochemistry for BRAF V600E was performed in colorectal cancers with loss of MLH1 protein expression. Relationship between MMR protein expression and clinicopathologic features was analyzed statistically. Results: Forty-four cases of 658 cases (6.7%) lost at least one MMR protein expression. Expression deficiency rates of MLH1, MSH2, MSH6 and PMS2 were 4.1%(27/658), 2.3%(15/658), 2.4% (16/658), and 4.3% (28/658), respectively. MMR expression deficiency mainly consisted of combined loss of MLH1/PMS2 (61.4%, 27/44) and MSH2/MSH6 (34.1%, 15/44). Two unique mutations were identified including one MSH6-deficient(2.3%, 1/44) and PMS2-deficient(2.3%, 1/44). Seven cases (25.9%, 7/27) had positive BRAF V600E expression, suggesting BRAF gene mutation related sporadic colorectal cancers. No correlation was observed between the expression of MMR and depth of tumor infiltration, lymph node metastasis, vascular tumor emboli, clinical stage or hematogenous metastasis (P>0.05). MMR status was associated with tumor cell differentiation, histological type and tumor location (P<0.01). Tumors with combined MLH1 and PMS2 loss were associated with mucinous differentiation (P=0.049, P=0.013) and located in the right hemi-colon (P=0.006, P=0.002). Combined MSH2 and PMS2 loss was related to gender, while loss of MSH2 protein was observed more frequently in female patients (P=0.048) and loss of PMS2 protein was seen more frequently in male patients (P=0.031). Conclusions: Patients with MMR protein deficiency have a younger onset age and poorly differentiated tumors. Most tumors are located in the right hemi-colon and have mucinous differentiation.目的： 探讨错配修复(mismatch repair，MMR)蛋白MLH1、MSH2、MSH6和PMS2在结直肠癌中的表达情况及其与患者临床病理特征之间的关系。 方法： 收集中国医科大学附属盛京医院2016年1月至2017年1月间658例连续的结直肠癌病例，患者中男性409例，女性249例；年龄20～92岁，平均年龄(63±5)岁。采用免疫组织化学EnVision法检测结直肠癌组织中MLH1、MSH2、MSH6和PMS2蛋白表达缺失的情况，和MLH1蛋白表达缺失的结肠癌病例中的BRAF突变，分析MMR蛋白表达缺失与结直肠癌患者临床病理特征之间的关系。 结果： 658例结直肠癌有44例(6.7%)发生MMR蛋白表达缺失，MLH1、MSH2、MSH6、PMS2蛋白表达缺失率分别为4.1%(27/658)、2.3%(15/658)、2.4%(16/658)、4.3%(28/658)。MMR蛋白表达缺失以MLH1与PMS2表达联合缺失(61.4%，27/44)、MSH2与MSH6表达联合缺失(34.1%，15/44)为主；PMS2和MSH6蛋白表达单独缺失的各有1例(2.3%，1/44)。进行BRAF V600E检测的27例MLH1蛋白缺失的病例中有7例(25.9%)为BRAF阳性，提示该7例患者可能存在因BRAF基因突变导致的MLH1蛋白表达缺失，属于散发型结直肠癌。结直肠癌组织中MMR蛋白表达缺失与肿瘤浸润深度、淋巴结转移、脉管癌栓、临床分期以及肿瘤血行转移无关(P>0.05)，与更低程度的肿瘤组织分化、组织学类型和发病部位以及肿瘤浸润淋巴细胞数目增加显著相关(P<0.01)；其中MLH1、PMS2蛋白表达缺失与组织学类型相关(P＝0.049，P＝0.013)，常伴黏液腺癌分化；MLH1、PMS2蛋白表达缺失多发生于右半结肠(P＝0.006，P＝0.002)；MSH2与MSH6蛋白表达缺失的患者发病年龄相对较小(P＝0.014，P＝0.023)；MSH2与PMS2蛋白表达缺失与性别相关，MSH2蛋白缺失多发生于女性(P＝0.048)，PMS2蛋白表达缺失多发生于男性(P＝0.031)。 结论： MMR蛋白缺失结直肠癌患者发病年龄低，组织分化程度低，发生部位多位于右半结肠，癌组织常伴有黏液腺癌分化。.