中文摘要：

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.

英文摘要：

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.