结直肠微乳头状癌错配修复缺陷及KRAS、NRAS、PIK3CA、BRAF基因突变的研究  

Mismatch repair deficiency and mutations of KRAS,NRAS,PIK3CA and BRAF genes in colorectal micropapillary carcinoma

作　　者：吴晨鹏[1] 李军 刘颖 李雪梅[1] 张志勇[1] 王磊[3] WU Chenpeng;LI Jun;LIU Ying;LI Xuemei;ZHANG Zhiyong;WANG Lei(Department of Pathology,Tangshan Gongren Hospital,Tangshan 063000,China;Department of Laboratory,Tangshan Gongren Hospital,Tangshan 063000,China;Department of Pathology,Tangshan People’s Hospital,Tangshan 063001,China)

机构地区：[1]唐山市工人医院病理科,唐山063000 [2]唐山市工人医院检验科,唐山063000 [3]唐山市人民医院病理科,唐山063001

出　　处：《临床与实验病理学杂志》2024年第12期1276-1281,共6页Chinese Journal of Clinical and Experimental Pathology

基　　金：河北省自然科学基金(H2022105001);河北省医学科学研究课题计划项目(20201515)。

摘　　要：目的探讨结直肠微乳头状癌(micropapillary carcinoma,MPC)的临床病理及分子特征,为结直肠MPC的诊断及个体化治疗提供依据。方法收集461例结直肠癌患者的临床病理及分子检测资料,其中结直肠MPC 56例,结直肠腺癌非特殊型(not otherwise specified,NOS)405例,应用免疫组化法检测4项错配修复蛋白MLH1、PMS2、MSH2、MSH6及p53蛋白的表达,采用ARMS-PCR法检测KRAS、NRAS、PIK3CA及BRAF基因热点突变情况,分析结直肠MPC与腺癌NOS临床病理及分子特征的差异。结果结直肠MPC脉管侵犯率及淋巴结转移率显著高于腺癌NOS(42.9%vs 23.0%,P=0.001;67.9%vs 46.2%,P=0.002);结直肠MPC错配修复缺陷发生率显著低于腺癌NOS(3.6%vs 13.8%,P=0.030);结直肠MPC的KRAS基因外显子2、3、4区域热点突变率显著高于腺癌NOS(58.9%vs 42.2%,P=0.018),尤其是KRAS G13D位点突变率(17.9%vs 8.1%,P=0.019)。结直肠MPC成分所占比例与临床病理及分子特征无关。结直肠MPC与腺癌NOS伴高级别肿瘤出芽的临床病理及分子特征无显著差异。结论结直肠MPC的临床病理及分子特征与腺癌NOS有差异,准确诊断该亚型可为治疗方案的制定及预后评估提供一定帮助。Purpose To investigate the clinicopathological and molecular features of colorectal micropapillary carcinoma(MPC),and to provide evidence for the diagnosis and individual treatment of colorectal MPC.Methods The clinicopathological and molecular data of 461 patients with colorectal cancer were collected retrospectively,including 56 cases of colorectal MPC and 405 cases of colorectal adenocarcinoma not otherwise specified(NOS).The expression of 4 mismatch repair proteins(MLH1,PMS2,MSH2,MSH6)and p53 protein was detected by immunohistochemistry.The hot spot mutations of KRAS,NRAS,PIK3CA and BRAF genes were detected by ARMS-PCR,to analyze the difference of clinicopathological and molecular features between colorectal MPC and adenocarcinoma NOS.Results The vessel invasion rate and lymph node metastasis rate of colorectal MPC were significantly higher than those of adenocarcinoma NOS(42.9%vs 23.0%,P=0.001;67.9%vs 46.2%,P=0.002).The incidence of mismatch repair deficiency in colorectal MPC was significantly lower than that in adenocarcinoma NOS(3.6%vs 13.8%,P=0.030).The hot spot mutation rate in exon 2,3 and 4 of KRAS gene in colorectal MPC was significantly higher than that in adenocarcinoma NOS(58.9%vs 42.2%,P=0.018),especially in KRAS G13D(17.9%vs 8.1%,P=0.019).The proportion of colorectal MPC components was not associated with clinicopathological and molecular features.There were no significant differences in clinicopathological and molecular features between colorectal MPC and adenocarcinoma NOS with high-grade tumor budding.Conclusion The clinicopathologic and molecular features of colorectal MPC are different from those of adenocarcinoma NOS,and the diagnosis of this subtype may provide help for the formulation of treatment plan and the evaluation of prognosis.

关 键 词：结直肠微乳头状癌 错配修复缺陷 KRAS NRAS PIK3CA BRAF 

分 类 号：R735.3[医药卫生—肿瘤]