Institute of Pathology, Kantonsspital St Gallen, St Gallen, Switzerland.
J Clin Pathol. 2011 Dec;64(12):1112-6. doi: 10.1136/jclinpath-2011-200265. Epub 2011 Oct 19.
To determine the frequency of HER2 genetic heterogeneity according to the recent American Society of Clinical Oncology (ASCO) and College of American Pathologists (CAP) definition (2009) in invasive breast carcinoma, and to identify clinicopathological features that characterise breast carcinomas with HER2 genetic heterogeneity.
530 invasive breast carcinomas were retrospectively analysed for HER2 genetic heterogeneity, and investigated for a potential association of HER2 genetic heterogeneity with other HER2 FISH findings, clinicopathological parameters, oestrogen/progesterone receptor expression and DNA cytometric parameters in breast carcinomas with an equivocal (2+) HER2 immunohistochemical score.
The overall frequency of HER2 genetic heterogeneity was 14.7% in a cohort of 218 consecutive breast carcinomas. HER2 genetic heterogeneity was most frequent in invasive breast carcinomas with an equivocal (2+) HER2 immunohistochemical score. Among the 151 carcinomas lacking HER2 amplification, 16.1% showed HER2 genetic heterogeneity. In an extended cohort of 345 carcinomas with a (2+) HER2 score, the frequency of HER2 genetic heterogeneity was 41%, and was associated with the absence of HER2 gene clusters, chromosome 17 polysomy, histological tumour grade, DNA ploidy category and 5c exceeding rate.
HER2 genetic heterogeneity according to the ASCO/CAP definition is frequent in breast carcinoma, and is most often present in carcinomas with an equivocal (2+) HER2 score. Many carcinomas with HER2 genetic heterogeneity have a negative HER2 amplification status, although they contain a significant number of tumour cells with HER2 gene amplification. Single cell scoring of the HER2/17 centromeric probe (CEP17) ratio is necessary to identify carcinomas with HER2 genetic heterogeneity, because they lack specific clinicopathological characteristics.
根据最近的美国临床肿瘤学会（ASCO）和美国病理学家学院（CAP）定义（2009 年），确定 HER2 基因异质性在浸润性乳腺癌中的频率，并确定具有 HER2 基因异质性的乳腺癌的临床病理特征。
回顾性分析了 530 例浸润性乳腺癌的 HER2 基因异质性，并研究了 HER2 基因异质性与其他 HER2 FISH 结果、临床病理参数、雌激素/孕激素受体表达和具有不确定（2+）HER2 免疫组织化学评分的乳腺癌的 DNA 细胞计量学参数之间的潜在相关性。
在连续 218 例乳腺癌队列中，HER2 基因异质性的总体频率为 14.7%。HER2 基因异质性在具有不确定（2+）HER2 免疫组织化学评分的浸润性乳腺癌中最为常见。在 151 例缺乏 HER2 扩增的乳腺癌中，16.1%显示 HER2 基因异质性。在 345 例具有（2+）HER2 评分的扩展队列中，HER2 基因异质性的频率为 41%，并与 HER2 基因簇缺失、17 号染色体多倍体、组织学肿瘤分级、DNA ploidy 类别和 5c 超过率有关。
根据 ASCO/CAP 定义，HER2 基因异质性在乳腺癌中很常见，并且最常存在于具有不确定（2+）HER2 评分的乳腺癌中。许多具有 HER2 基因异质性的乳腺癌具有阴性的 HER2 扩增状态，尽管它们含有大量具有 HER2 基因扩增的肿瘤细胞。HER2/17 着丝粒探针（CEP17）比值的单细胞评分对于识别具有 HER2 基因异质性的乳腺癌是必要的，因为它们缺乏特定的临床病理特征。
