摘要
目的分析结直肠癌组织KRAS、NRAS、BRAF和PIK3CA基因突变与临床病理因素及MMR蛋白表达的相关性。方法采用扩增阻碍突变系统(ARMS)和免疫组化法对122例结直肠癌石蜡组织进行回顾性分析。结果 122例结直肠癌组织中KRAS、NRAS、BRAF和PIK3CA基因突变率分别为48.4%(59/122)、4.1%(5/122)、5.7%(7/122)和5.7%(7/122)。检出KRAS与PIK3CA双突变病例3例,BRAF与PIK3CA双突变1例,未发现BRAF与KRAS或NRAS基因同时突变病例。女性患者KRAS突变率高于男性患者(P<0.05),低分化腺癌KRAS突变率高于高、中分化腺癌(P<0.001)。女性患者、有淋巴结转移者和MLH1蛋白表达缺失者与男性患者、无淋巴结转移和MLH1表达者比(P<0.05),PMS2蛋白表达缺失者比表达者的BRAF突变率更高。黏液腺癌PIK3CA突变率较其他肿瘤组织学类型高(P<0.05)。结论该4种基因在结直肠癌的突变率依次为KRAS、 BRAF、PIK3CA、NRAS,不存在4种基因全突变及3种基因突变。BRAF与KRAS、NRAS基因突变存在相互排斥现象。KRAS、BRAF、PIK3CA基因突变与结直肠癌临床病理特征存在相关性。
Objective To retrospectively analyze the correlation between KRAS,NRAS,BRAF,PIK3 CA gene mutations and the clinicopathological features,as well as the relationship between these genetic mutations and mismatch repair(MMR)protein expression in colorectal cancer(CRC).Methods We detected KRAS,NRAS,BRAF,PIK3 CA gene mutations in 122 paraffin-embedded CRC tissues by amplification refractory mutation system(ARMS).The MMR proteins expression was investigated by immunohistochemistry.Results The mutational frequency of KRAS,NRAS,BRAF and PIK3 CA was 48.4%(59/122),4.1%(5/122),5.7%(7/122),and 5.7%(7/122),respectively.There were 3 cases harbored both KRAS and PIK3 CA mutations,and 1 case carried BRAF and PIK3 CA mutations.KRAS mutations were more likely to occur in female(P<0.05),and poor differentiation tumor(P<0.05).BRAF mutations were related with female(P<0.05),lymphatic metastasis(P<0.05),MLH1 deficiency(P<0.05),and PMS2 deficiency(P<0.01).PIK3 CA mutation was correlated with mucinous adenocarcinoma(P>0.05).Conclusion The most frequently mutated gene is KRAS,followed by BRAF,PIK3 CA,and NRAS.There is no case with 3 or 4 genetic mutations at the same time.BRAF,KRAS and NRAS are mutated mutually exclusive.KRAS,BRAF and PIK3 CA gene mutations are significantly related to the clinicopathological features of CRC.
作者
孙林雍
江丹
何度
唐源
陈杰
陈昶
邹艳
张文燕
SUN Lin-yong;JIANG Dan;HE Du;TANG Yuan;CHEN Jie;CHEN Chang;ZOU Yan;ZHANG Wen-yan(Department of Pathology,West China Hospital,Sichuan University,Chengdu 610041,China)
出处
《诊断病理学杂志》
2019年第6期354-358,共5页
Chinese Journal of Diagnostic Pathology
基金
国家自然科学青年基金资助(基金号81401990)
