PIK3CA和TP53基因突变与乳腺癌分子分型及组织学分级相关性的研究  

Study on the correlation between PIK3CA/TP53 gene mutations and molecular typing and histological grading of breast cancer

作　　者：杨波[1] 张晓燕[2] 曾鸿[3] 刘海量 刘彦慧[2] 韩淑珍[5] YANG Bo;ZHANG Xiaoyan;ZENG Hong;LIU Hailiang;LIU Yanhui;HAN Shuzhen(Department of Breast Surgery,Dongguan Maternal and Child Health Hospital,Dongguan,Guangdong 523000,P. R. China;Center of Prenatal Diagnosis,Dongguan Institute of Reproductive and Genetic Research,Dongguan Maternal and Child Health Hospital,Dongguan,Guangdong 523000,P. R. China;Department of Pathology,Dongguan Maternal and Child Health Hospital,Dongguan,Guangdong 523000,P. R. China;Capital Bio Technology Inc,Dongguan,Guangdong 523808,P. R. China;Department of Pathology,Dongguan Houjie Hospital,Dongguan,Guangdong 523000,P. R. China)

机构地区：[1]东莞市妇幼保健院乳腺科,广东东莞523000 [2]东莞市妇幼保健院产前诊断中心 东莞市生殖与遗传研究所,广东东莞523000 [3]东莞市妇幼保健院病理科,广东东莞523000 [4]东莞博奥木华基因科技有限公司,广东东莞523808 [5]东莞市厚街医院病理科,广东东莞523000

出　　处：《中国普外基础与临床杂志》2019年第5期573-578,共6页Chinese Journal of Bases and Clinics In General Surgery

基　　金：东莞市社会科技发展项目(项目编号:2015108101030)

摘　　要：目的分析乳腺癌突变基因与乳腺癌分子分型和组织学分级的关系,为进一步治疗提供参考依据。方法回顾性收集2016年2月至2017年8月期间广东省东莞市妇幼保健院和东莞市厚街医院诊治的46例未行化疗的乳腺癌患者的病理切片标本,采用免疫组织化学染色技术检测肿瘤组织中雌激素受体(ER)、孕激素受体(PR)及人表皮生长因子受体-2(HER-2)的表达,并对病理切片组织进行分级。使用多重PCR技术,扩增所选择的50个肿瘤相关基因的207个热点突变区域,然后采取高通量的半导体测序平台(SSP)进行检测。结果 46例乳腺癌患者的组织学分级:Ⅰ级8例,Ⅱ级18例,Ⅲ级20例;ER/PR/HER-2状态分型:Luminal A型9例,Luminal B型23例,HER-2过表达型9例,besal-like型5例。所有样本共检测到8种基因的33个位点突变,包括AKT1、APC、BRAF、CDKN2A、KRAS、PTEN、PIK3CA和TP53基因,其中PIK3CA基因突变24例,TP53基因突变18例,CDKN2A基因突变2例,其余突变基因各检出1例。乳腺癌的总基因突变情况与组织学分级和分子分型均无关(P>0.05);PIK3CA基因突变与乳腺癌的组织学分级相关,组织学分级越低PIK3CA基因的突变频率越高(P<0.05)。结论 PIK3CA基因在组织学分级Ⅰ级患者中的突变率明显增高。Objective To provide reference for further treatment by analyzing the relationship between mutant genes of breast cancer and histological classification and molecular typing of breast cancer. Methods Retrospectively collectted the pathological specimens of 46 breast cancer patients who treated by the Dongguan Maternal and Child Health Hospital and the Dongguan Houjie Hospital between February 2016 and August 2017 without chemotherapy. Among the selected 46 breast cancer patients, we detected tumor tissue estrogen receptor (ER)/ pregnancy hormone receptor (PR)/human epidermal growth factor receptor-2 (HER-2) status by immunohistochemistry and classified the pathological tissue section. By using multiple PCR techniques, we detected 207 hot mutation regions of the 50 extended tumor-related genes on the semiconductor sequencing platform. Results There were 8 cases of grade Ⅰ, 18 cases of grade Ⅱ, 20 cases of grade Ⅲ in 46 breast cancer patients according to histological grade. Of the 46 cases, there were 23 cases of Luminal B, 9 cases of Luminal A, 9 cases of HER-2 (+), 5 cases of type besal-like according to ER/PR/HER-2 expression status. Moreover, we found that there were 33 gene locus mutations of 8 genes, including AKT1, APC, BRAF, CDKN2A, KRAS, PTEN, PIK3CA, and TP53. Among of them, the mutation of PIK3CA gene took the most of 24 cases, followed by TP53 (18 cases), 2 cases of CDKN2A gene mutation, and 1 case in the remaining four types of genes respectively, we found that the gene mutations of breast cancer were not related to the histological classification and molecular type (P>0.05), the PIK3CA gene mutation was related to the histological classification of breast cancer, the lower the histological classification level, the higher PIK3CA gene mutation rate (P<0.05). TP53 gene mutation was not related to histological grading and molecular type (P>0.05). Conclusions The PIK3CA gene mutation rate in patients with histological grading Ⅰ level increased significantly. The combination of PIK3CA gene mutatio

关 键 词：乳腺癌 突变谱 基因筛查 高通量测序 

分 类 号：R737.9[医药卫生—肿瘤]