南方医科大学学报

南方医科大学学报 ›› 2020, Vol. 40 ›› Issue (11): 1645-1650.doi: 10.12122/j.issn.1673-4254.2020.11.17

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微卫星不稳定性类型及临床病理特征： 基于1394例结直肠癌患者的标本检测

黎相照，刘焕娇，梁敏仪，陈慧慧，梁 莉   

  • 出版日期:2020-11-20 发布日期:2020-11-23

Clinicopathological features and types of microsatellite instability in 1394 patients with colorectal cancer

  • Online:2020-11-20 Published:2020-11-23

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摘要： 目的 研究微卫星不稳定性（MSI）结直肠癌病人错配修复（MMR）基因突变的类型和临床病理特征。方法 收集南方医科大学南方医院2016~2018年1394例结直肠癌病人石蜡标本，采用免疫组化染色技术检测MMR蛋白；MSI基因检测106例dMMR病例，46例肿瘤细胞呈异质性表达的pMMR病例和147例随机选择的pMMR病例；分析错配修复蛋白缺失与结直肠癌临床病理特征参数的关系；比较两种方法检测结果的一致性。结果 MMR蛋白缺失发生率占总结直肠癌病人的7.6%，缺失类型主要为MLH1、PMS2双缺失，占总缺失的55.7%；MMR蛋白缺失与结直肠癌患者的年龄、发生部位、大体分型、肿瘤大小、组织学分型、分化程度和临床TNM分期均有关（P<0.05），而与患者的性别无关（P=0.47）；dMMR结直肠癌病人具有典型的临床病理特征：MMR蛋白缺失在年龄<50岁、右半结肠、肿瘤直径>6 cm、腺癌伴粘液腺癌或粘液分泌的混合型癌、低分化腺癌和TNM分期Ⅰ/Ⅱ期组的发生率高；免疫组化和PCR-毛细管电泳法在结直肠癌微卫星不稳定性检测结果一致性为98.7%。结论 微卫星不稳定性错配修复蛋白表达缺失（dMMR）在结直肠癌的主要类型为MLH1、PMS2双缺失，具有典型的临床病理特征，其发生率低于西方报道；免疫组化和PCR毛细管电泳法的检测结果显示高度的一致性。

关键词: 结直肠癌；微卫星不稳定；错配修复；免疫组化, PCR-毛细管电泳

Abstract: Objective To explore the clinicopathological features and types of genic mutations in DNA mismatch repair (MMR) in colorectal cancer (CRC). Methods Immunohistochemistry was used to determine the expression of MMR proteins in 1394 patients with CRC, and PCR-capillary electrophoresis (PCR-CE) was used to detect microsatellite instability (MSI) in 106 cases of defective MMR (dMMR), 46 cases of proficient MMR (pMMR) with heterogeneous expression and 147 randomly selected cases of pMMR. The relationship between the expressions of MMR proteins and the clinicopathological features of the patients was evaluated. The consistency between the results of immunohistochemistry and PCR-CE was assessed. Results Immunohistochemical staining showed an incidence of dMMR of 7.6% in the patients. The main type of dMMR was codeletion of MLH1 and PMS2, accounting for 55.7% of the total dMMR cases. The deletion of MMR proteins was significantly correlated with the patients' age, tumor location, tumor size, gross type, histological type, degree of differentiation, lymph node status and TNM stage (P<0.05), but not with gender (P>0.05). The total accordance rate of immunohistochemistry and PCR-CE was 98.7% in these patients. Conclusion The main type of dMMR is co-deletion of MLH1 and PMS2 in patients with colorectal cancer. dMMR colorectal cancer has typical clinicopathological features and a lower incidence in China than in Western countries. The results of immunohistochemistry and PCR-CE are highly consistent for detecting dMMR in colorectal cancer patients.

Key words: colorectal cancer, microsatellite instability, mismatch repair, immunohistochemistry, polymerase chain reactioncapillary electrophoresis