BRCA1、Ki67在不同分子分型乳腺癌中的表达及临床病理意义

Clinical Pathological Significance of BRCA1 and Ki67 Expression in Different Molecular Classification of Breast Cancer

目的探讨BRCA1、Ki67在不同分子分型乳腺癌进展中的作用、临床病理意义。方法应用荧光原位杂交技术(FISH),对免疫组化方法检测Her2为2+以上(包含2+)的肿瘤蜡块做进一步检测,FISH检测出阳性表达的肿瘤蜡块定义为Her2最终阳性表达,并依据《2013版中国抗癌协会乳腺癌诊治指南与规范的标准》对乳腺浸润性导管癌进行分子分型,依据分子分型将乳腺癌分为五类Luminal A型,Luminal B like型,Luminal B样型,Her2过表达型和基底细胞样型,各分型分别选取20例,总共100例乳腺浸润性导管癌病例。采用免疫组化二步法对入选病例的肿瘤组织进行BRCA1及Ki67蛋白的检测。结果 BRCA1蛋白阳性表达率在Luminal A型组,Luminal B like型组,Luminal B样型组,Her2过表达型组,基底细胞样型组中差异具有明显显著性(P<0.05);BRCA1蛋白表达与年龄、肿瘤大小、肿瘤距乳头距离、组织学分级、腋窝淋巴结转移情况、ER/PR状态、Her2状态均无关(P均>0.1);Ki67高指数表达率在Luminal A型组,Luminal B like型组,Luminal B样型组,Her2过表达型组,基底细胞样型组中差异具有明显显著性(P<0.05);年龄组≤59岁的Ki67高指数表达率较年龄组≥60岁的增高,差异有统计学意义(P<0.1);ER/PR阴性组和Her2阳性组的Ki67高指数表达率较ER/PR阳性组和Her2阴性组增高,差异具有统计学意义(P<0.1);Ki67表达与肿瘤大小、肿瘤距乳头距离、组织学分级、腋窝淋巴结转移等临床病理指标无相关性(P均>0.1);BRCA1与Ki67在各亚型乳腺癌中的表达呈负相关性(P<0.05)。结论联合检测BRCA1和Ki67对不同分子分型乳腺癌有一定的预测预后价值。

Objective To investigate the effect of BRCA1 and Ki67 in different molecular subtypes of breast cancer,and its clinical pathological significance.Methods Testing the tumor wax block by using FISH method which were Her2 2 ＋ or 3 ＋detected by immunohistochemical method.FISH method showed the positive expression of tumor wax block was defined as Her2 positive expression,eventually.Classificating breast invasive ductal carcinoma in molecular classification according to the 2013 edition of the Chinese anti-cancer association guidelines and normative standard of diagnosis and treatment of breast cancer,and the breast cancer can be divided into 5 subtypes in molecular classification： Luminal A subtype group,Luminal B like subtype group,Luminal B subtype group,Her2 over-expression subtype group,basal-like subtype group.Select 15 cases from each subtype,total of 75 cases of breast invasive ductal carcinoma.Detected BRCA1 and Ki67 protein in each tumor tissues by immunohistochemical SP method and analyzed its relationship with the clinical pathological indicators.Results Positive expression rate of BRCA1 protein had obviously significant difference in the Luminal A subtype group,Luminal B like subtype group,Luminal B subtype group,Her2 over-expression subtype group and basal-like subtype group（P〈0.05）; There were no significant differences with the expression of BRCA1 protein and age,tumor size,tumor distance from the nipple,histological grade and axillary lymph node metastasis,ER/PR status as well as Her2 status（P〉0.1）; High index expression rate of Ki67 had obviously significant difference in the Luminal A subtype group,Luminal B like subtype group,Luminal B subtype group,Her2 over-expression subtype group and basallike subtype group（P〈0.05）; High index expression rate of Ki67 in the ≤59 group was more than ≥60 group,the difference was statistically significant（P〈0.1）; High index expression rate of Ki67 in ER/PR negative group and Her2 positive group was more than that in ER/PR positive group and her2-negative group,the difference had statistical significance（P〈0.1）; There were no significant differences in the expression of Ki67 protein and tumor size,tumor distance from the nipple,histological grade as well as axillary lymph node metastasis（P〉0.1）; The expression of BRCA1 and Ki67 in different subtypes of breast cancer showed a negative correlation（P〈0.05）.Conclusion Joint detection of BRCA1 and Ki67 in different molecular classification of breast cancer might play an important role in predicting clinical outcomes.