散发性结直肠癌癌组织中错配修复蛋白和nm23蛋白表达与临床病理特征的关系-东南大学学报医学版

散发性结直肠癌癌组织中错配修复蛋白和nm23蛋白表达与临床病理特征的关系

单位：1. 唐山市工人医院病理科, 河北唐山 063000;
2. 唐山市工人医院肿瘤外科, 河北唐山 063000

分类号：R735.3

出版年·卷·期（页码）：2018·37·第四期（642-648）

摘要：

目的：分析散发性结直肠癌癌组织中错配修复蛋白（MMRP）和nm23蛋白表达与临床病理特征的关系以及两者相关性，旨在为治疗散发性结直肠癌患者提供参考。方法：选取2014年8月至2017年1月本院存档的680例手术切除散发性结直肠癌标本。采用免疫组化法以及组织芯片检测MMRP以及mm23蛋白的表达情况，将4种MMRP中的1种以上表达缺失定为微卫星不稳定组（MSI组），全部阳性表达设为微卫星稳定（MSS组）组。分析MMRP与mm23的表达与临床病理特征的相关性以及两种蛋白之间的相关性。结果：在本组研究中，MMRP阳性者有605例，表达缺失者有75例，缺失率为11.03%；其中MLH1缺失11例（14.67%）、PMS2缺失5例（6.67%）、MSH2缺失6例（8.00%）及MSH6表达缺失3例（4.00%），MLH1联合PMS2表达缺失19例（25.33%），MSH2联合MSH6表达缺失12例（16.00%），MLH1联合MSH2表达缺失5例（6.67%），MLH1联合MSH6表达缺失3例（4.00%），MSH2联合PMS2表达缺失3例（4.00%），MLH1联合MSH2、MSH6表达缺失2例（2.67%），MSH2联合MSH6、PMS2表达缺失3例（4.00%），4种表达均缺失3例（4.00%）；nm23阴性表达278例（40.88%），阳性表达402例（59.12%）；MSI表达情况在不同年龄、肿瘤部位、肿瘤直径、临床分期、淋巴结转移、组织类型等患者间存在差异（P<0.05），nm23表达情况在不同组织类型、远处转移、浸润深度、大体分型等患者间存在差异（P<0.05）；经Spearman分析得出，MSI与nm23呈正相关（r=0.563，P<0.001）。结论：（1）在散发性结直肠癌患者中存在MMRP缺失，并且MLH1、PMS2缺失表达较MSH2和MSH6多见；（2）MSI及nm23与散发性结直肠临床病理特征关系密切，对散发性结直肠癌的预测以及恶性程度的评估具有参考价值，并且两者呈正相关，可能参与散发性结直肠癌的发生发展过程。

Objective:To investigate the correlation of the expression of mismatch repair protein and nm23 protein with clinicopathological features in sporadic colorectal cancer and relationship between mismatch repair protein and nm23 protein to provide a reference for the treatment of sporadic colorectal cancer. Methods:680 specimens from surgical resection of sporadic colorectal cancer in our hospital from August 2014 to January 2017 were selected. The immunohistochemistry and tissue microarray were used to detect MMRP and mm23 protein. The specimen with more than 1 kinds of MMRP deficiency was dividend into microsatellite instability (MSI) group, and with 4 kinds of MMRP positive expression into microsatellite stable (MSS) group. The correlation between the expression of MMRP and mm23 and clinicopathological features and the correlation between the two proteins were analyzed. Results:In this study, there were 605 cases with positive MMRP and 75 cases with the deficiency expression MMRP and the loss rate was 11.03%. There were 11 (14.67%) cases with MLH1 deletion, 5 (6.67%) cases with PMS2 deletion, 6(8.00%) cases with MSH2 deletion and 3 (4.00%) cases with MSH6 deletion. There were 19 (25.33%) cases with MLH1 combined with PMS2 expression deletion, 12 (16%) cases with MSH2 combined with MSH6 deletion, 5 cases (6.67%) with MLH1 combined with MSH2 deletion, 3 (4.00%)cases with MLH1 combined with MSH6 deletion, 3 (4.0%)cases MSH2 combined with PMS2 deletion, 2 (2.67%)cases with MLH1 combined with MSH2 and MSH6 deletion and 3 cases (4%) with MSH2, MSH6 and PMS2 deletion. There 3 (4.00%) cases with 4 protein deletion. There were 278 (40.88%) cases with nm23 negative expression and 402 (59.12%) cases with positive expression. The expressions of MSI in patients with different age, tumor location, tumor diameter, clinical stage, lymph node metastasis, histological type were significantly different (P<0.05). The nm23 expressions in patients with different pathological type, distant metastasis, depth of invasion, gross type were significantly different (P<0.05). Spearman correlation analysis showed that there was a positive correlation between MSI and nm23 (r=0.563, P<0.001). Conclusion:(1) There is mismatch repair protein deficiency in patients with sporadic colorectal cancer, and the expression deficiency in MLH1 and PMS2 is higher than that of MSH2 and MSH6; (2) There is a close relationship between MSI and nm23 and clinicopathological features of sporadic colorectal, which has a reference value in predicting sporadic colorectal cancer and malignant degree evaluation. MSI and nm23 protein were positively correlated, which may participate in the occurrence and development of sporadic colorectal cancer.

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