26 280例结直肠癌患者MLH1和PMS2基因表达情况及临床病理特征的多中心回顾性研究

目的研究MLH1和PMS2蛋白表达情况与临床病理特征。 方法本研究纳入2010年1月至2018年12月包括中国医学科学院肿瘤医院在内7家医院的结直肠癌数据平台的患者205 071人次，其中26 280例免疫组化信息和病例信息满足研究标准。分析MLH1和PMS2基因蛋白表达情况与患者发病年龄、性别、肿瘤大小、病理分期等因素的关系。 结果MLH1缺失率4%，PMS2缺失率3.25%。两种蛋白表达缺失的患者男女比例差异存在统计学意义（均P<0.05），其发病年龄均小于正常表达组患者（均P<0.0001）。其第二原发癌的发病率也高于正常表达组（均P<0.0001）。MLH1和PMS2蛋白表达缺失的患者肿瘤最大径大于正常表达组（均P<0.0001），清扫淋巴结总数目也高于正常表达组（均P<0.0001）。此外，与正常组相比，MLH1表达缺失组呈现明显家族聚集倾向（P=0.001）。而在部位上，肿瘤部位发生在右半结肠的患者数据显示，MLH1和PMS2蛋白缺失的发生率高于蛋白表达正常组。肿瘤分期方面，MLH1和PMS2蛋白的T分期在表达缺失组与正常组差异具有统计学意义（均P<0.0001），M分期中，PMS2蛋白缺失患者的远处转移率低于正常组患者（P=0.0008）。 结论MLH1与PMS2表达缺失的患者发病年龄更早，肿瘤体积大，右半结肠比例相对较高，第二原发癌的发生率更高，伴有更高的淋巴结清扫数目，且与病理分期存在密切关联。

A multi-center retrospective study of MLH1 and PMS2 gene expression and clinicopathological features in 26 280 patients with colorectal cancer

ObjectiveTo study the expression of MLH1 and PMS2 proteins and the characteristics of clinicopathological features. MethodsA total of 205 071 patients with colorectal cancer data from 7 hospitals including the Chinese Academy of Medical Sciences Cancer Hospital from January 2010 to December 2018 were included in the study. 26 280 immunohistochemical information and case information met the research criteria. The relationship between MLH1 and PMS2 gene protein expression and age, sex, tumor size, pathological stage and other factors were analyzed. ResultsThe MLH1 deletion rate was 4%, and the PMS2 deletion rate was 3.25%. There was a statistically significant difference in the ratio of male to female in the two patients with loss of protein expression (both P<0.001), and the age of onset was smaller than that in the normal expression group (both P<0.001). The incidence of the second primary cancer was also higher than that of the normal expression group (both P<0.001). The maximal tumor diameter of patients with MLH1 and PMS2 protein expression was greater than that of the normal expression group (all P<0.001), and the total number of lymph nodes cleared was also higher than the normal expression group (both P<0.001). In addition, the MLH1 expression-deficient group showed a clear tendency to familial aggregation compared to the normal group (P=0.001). At the site, the incidence of MLH1 and PMS2 protein deletions in the right colon was higher than in the normal expression group. In terms of tumor stage, the T stage of MLH1 and PMS2 protein was significantly different between the expression loss group and the normal group (P<0.001). In the M stage, the distant metastasis rate of patients with PMS2 protein deletion was lower than that of the normal group (P<0.001). ConclusionPatients with loss of MLH1 and PMS2 expression have earlier onset age, larger tumor volume, higher proportion of right colon, higher incidence of second primary cancer, higher number of lymph node dissection, and pathological staging. There is a close correlation.