Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA.
J Clin Pathol. 2013 Aug;66(8):649-54. doi: 10.1136/jclinpath-2012-201403. Epub 2013 Mar 28.
HER2/neu (HER2) is a significant prognostic marker for breast carcinomas. Recently, new guidelines defining HER2 genetic heterogeneity (GH) were published by the College of American Pathologists.
To determine the prevalence of HER2 GH as defined in primary invasive breast carcinoma, to determine its relationship with prognostic variables and to investigate its impact on concurrent axillary metastasis.
235 consecutive infiltrating breast carcinomas were evaluated for GH (defined as presence of 5-50% of neoplastic cells with HER2/CEP17 ratio >2.2) using fluorescence in situ hybridisation. Pathological features of carcinomas with GH were compared with those lacking GH. GH was also evaluated in a subset of 37 paired primary carcinomas and its concurrent axillary nodal metastases using dual in situ hybridisation.
HER2 GH was noted in 27% of HER2 negative breast carcinomas. These carcinomas demonstrated aggressive characteristics (larger size, higher grade and greater incidence of lymph node metastasis) in comparison with HER2 negative cases without GH. Higher levels of GH were associated with the equivocal HER2 status. GH was maintained in the concurrent lymph node metastases with some variations; however, two cases with clusters of HER2 amplified cells in the primary carcinoma showed HER2 amplification in the nodal metastasis.
HER2 GH is present in 27% of breast carcinomas, portends an aggressive phenotype and contributes to the equivocal HER2 status. Evaluation of the HER2 status in nodal metastasis of select primary carcinomas with GH may be beneficial before treatment selection.
HER2/neu（HER2）是乳腺癌的重要预后标志物。最近，美国病理学家学院发布了新的指南，定义了 HER2 基因异质性（GH）。
确定原发性浸润性乳腺癌中 HER2 GH 的患病率，确定其与预后变量的关系，并研究其对同期腋窝转移的影响。
使用荧光原位杂交技术评估 235 例连续浸润性乳腺癌的 GH（定义为存在 5-50%的肿瘤细胞，HER2/CEP17 比值>2.2）。比较 GH 阳性和 GH 阴性的乳腺癌的病理特征。还使用双重原位杂交技术在 37 对原发性乳腺癌及其同期腋窝淋巴结转移的亚组中评估 GH。
HER2 阴性乳腺癌中发现 27%存在 HER2 GH。与 GH 阴性病例相比，这些乳腺癌具有更大的肿瘤大小、更高的分级和更高的淋巴结转移发生率等侵袭性特征。较高的 GH 水平与 HER2 状态不确定有关。GH 在同期淋巴结转移中得以维持，但存在一些变化；然而，在原发性癌中存在簇状 HER2 扩增细胞的两个病例中，淋巴结转移显示 HER2 扩增。
HER2 GH 存在于 27%的乳腺癌中，预示着侵袭性表型，并导致 HER2 状态不确定。在选择治疗前，对存在 GH 的特定原发性乳腺癌的淋巴结转移进行 HER2 状态评估可能有益。
