Department of Pathology, Azienda Ospedaliero-Universitaria S. Maria della Misericordia, , Udine, Italy.
J Clin Pathol. 2013 Dec;66(12):1070-5. doi: 10.1136/jclinpath-2013-201506. Epub 2013 Aug 1.
HER2NEU gene amplification is present in the majority of invasive breast carcinomas that have HER2 protein overexpression. A subset of breast cancers harbour an increased chromosome 17 (CEP17) copy number (polysomy 17). We investigated the clinicopathologic significance of polysomy 17 in correlation with various histological parameters and HER2NEU gene amplification.
We collected the surgical specimens of 266 consecutive cases of primary invasive breast carcinomas. HER2NEU gene status and CEP17 copy numbers were assessed by fluorescent in situ hybridisation (FISH). Chromosome 17 polysomy was determined by the presence of ≥3 average CEP17 signals per nucleus.
63 tumours (23.7%) harboured polysomy 17. Carcinomas with polysomy 17 were associated with adverse histological indicators including high histological grade, high nuclear grade, poor Nottingham Prognostic Index, advanced local tumour extent and progesterone receptor negativity. Polysomy 17 was common to HER2NEU amplified and unamplified tumours, and more frequently observed in HER2NEU unamplified (71.4%) cases.
In the absence of the gene amplification, HER2 protein overexpression may be explained by other mechanisms including polysomy 17.
HER2NEU 基因扩增存在于大多数具有 HER2 蛋白过表达的浸润性乳腺癌中。一部分乳腺癌具有增加的染色体 17(CEP17)拷贝数(三体性 17)。我们研究了三体性 17 与各种组织学参数和 HER2NEU 基因扩增的相关性的临床病理意义。
我们收集了 266 例连续原发性浸润性乳腺癌的手术标本。通过荧光原位杂交(FISH)评估 HER2NEU 基因状态和 CEP17 拷贝数。染色体 17 三体性通过每个细胞核中存在≥3 个平均 CEP17 信号来确定。
63 个肿瘤(23.7%)存在三体性 17。具有三体性 17 的癌与不良的组织学指标相关,包括高组织学分级、高核分级、不良的诺丁汉预后指数、局部肿瘤进展程度较高和孕激素受体阴性。三体性 17 常见于 HER2NEU 扩增和未扩增的肿瘤,并且在 HER2NEU 未扩增(71.4%)的病例中更常见。
在没有基因扩增的情况下,HER2 蛋白过表达可能通过其他机制解释,包括三体性 17。