乳腺癌HER2基因遗传异质性与其临床病理特征的相关性研究  

Association of HER2 genetic heterogeneity with elinicopathological characteristics in breast cancer

作　　者：杨壹羚[1] 范宇[1] 郎荣刚[1] 谷峰[1] 付丽[1] 

机构地区：[1]天津医科大学附属肿瘤医院乳腺病理研究室教育部乳腺癌防治重点实验室天津市肿瘤防治重点实验室,300060

出　　处：《中华医学遗传学杂志》2010年第5期540-545,共6页Chinese Journal of Medical Genetics

基　　金：国家自然科学基金（30470667,30600225）;教育部长江学者乳腺癌创新团队支持计划（IRT0743）;科技部十一五“863”计划重大项目（2006AA02A249）;中国博士后科学基金（20090450772）

摘　　要：目的 介绍乳腺癌患者HER2基因扩增的瘤内遗传异质性（genetic heterogeneity,GH）现象,并探讨HER2基因GH与临床病理学参数间的相关性,寻找与HER2基因GH现象密切相关的病理学因素.方法 整理100例浸润性乳腺癌患者分期、组织学分型、分子分型等临床数据,应用免疫组化技术（immunohistochemistry,IHC）检测HER2、雌激素受体α（estrogen peceptor α,ERα）和孕激素受体（progesterone receptor,PR）蛋白表达,用荧光原位杂交（fluorescence in situ hybridization,FISH）技术检测HER2基因扩增情况,并分析HER2基因异质性与临床病理参数间的关系.结果 100例乳腺癌患者中有20%的病例（20/100）存在HER2基因GH现象.在瘤内异质性样本中,扩增细胞所占比例≥25%的样本组其FISH结果阳性率明显高于扩增细胞＜25%的样本组（P=0.012）.HER2蛋白的表达程度（P=0.004）和ER蛋白表达（P=0.002）与HER2基因GH现象显著相关.结论 HER2基因GH现象最易出现于HER2蛋白轻到中度表达、ER蛋白表达的乳腺癌组织,故而对于具有上述病理学特征的患者进行FISH检测时应特别注意GH现象,以免遗漏阳性细胞或者只计数阳性细胞,而给出不准确的FISH结果.Objective To introduce the College of American Pathologists/American College of Medical Genetics Cytogenetics Resource Committee criteria for genetic heterogeneity （GH） in HER2 testing, and investigate the clinicopathological significance of HER2 genetic heterogeneity in invasive breast cancer. Methods The clinical parameters of 100 cases of invasive breast carcinomas were collected. HER2 expression level and HER2 gene copy number in formalin-fixed and paraffin embedded tumor samples were detected by immunohistochemistry （IHC） and fluorescence in situ hybridization （FISH）, and the relationship between HER2 gene GH and clinicopathological characteristics were analyzed. Results Among the 100 patients, HER2 gene GH was observed in 20 （20%） cases. When the number of HER2 amplified cells was more than 25 %, the frequencies of FISH positive were higher than those cases with less than 25 % HER2 amplified cells. The results showed that HER2 gene GH was associated with the degree of HER2 protein expression （P= 0. 004）, and ER expression （P = 0. 002）. Conclusion HER2 gene GH may be correlated with the HER2 protein IHC 1＋/2＋, and ER expression in breast carcinoma. It is important for doctors to avoid ignoring or only counting FISH positive cells leading to incorrect diagnosis for these patients.

关 键 词：乳腺肿瘤 HER2基因 遗传异质性 

分 类 号：R686[医药卫生—骨科学]