Department of Breast Cancer Pathology and Research Laboratory, Key Laboratory of Breast Cancer Prevention and Therapy (Ministry of Education), Tianjin Medical University Cancer Institute & Hospital, Huanhuxi Road, Tiyuanbei, Hexi District, Tianjin 300060, China.
Breast Cancer Res Treat. 2012 Aug;134(3):1095-102. doi: 10.1007/s10549-012-2046-0. Epub 2012 Apr 5.
In 2009, ASCO/CAP expanded its human epidermal growth factor receptor type 2 (HER2) testing guideline to define HER2 genetic heterogeneity (GH). However, the clinical significance of GH is unclear. We investigated the impact of HER2 GH on HER2 testing and studied its clinicopathologic significance. Paraffin-embedded tumor tissues of surgical resections of 617 non-consecutive breast carcinoma patients were studied by routine HER2 fluorescence in situ hybridization (FISH). HER2 GH was evaluated, and the results were correlated with HER2 protein expression by immunohistochemistry and HER2 gene amplification by FISH, and with various clinicopathologic parameters. HER2 GH was observed in 15.2 % (94/617) of the patients. It was associated with low-to-middle level of HER2 expression, and with none-to-low level of HER2 gene amplification. Among the 17 patients with equivocal HER2 FISH results, 35.3 % (6/17) of tumors displayed GH. In contrast with HER2-positive tumors without GH, tumors with HER2 GH demonstrated significant association with lower histologic grade, smaller tumor size, and proclivity to hormone receptor expression. HER2 GH is a substantial cause of equivocal HER2 testing results of breast cancer by FISH. Tumors with HER2 GH showed that biologic features resemble more of HER2-negative tumors than HER2-positive tumors without GH. The findings indicate a need of the guidelines to clarify whether tumors with HER2 GH truly benefit from HER2-targeted therapy of breast cancer.
2009 年，ASCO/CAP 扩大了人表皮生长因子受体 2（HER2）检测指南，以定义 HER2 基因异质性（GH）。然而，GH 的临床意义尚不清楚。我们研究了 GH 对 HER2 检测的影响，并研究了其临床病理意义。对 617 例非连续乳腺癌手术切除的石蜡包埋肿瘤组织进行常规 HER2 荧光原位杂交（FISH）检测。评估了 HER2 GH，并将其结果与免疫组化检测的 HER2 蛋白表达和 FISH 检测的 HER2 基因扩增以及各种临床病理参数进行了相关性分析。在 617 例患者中观察到 15.2%（94/617）存在 HER2 GH。它与低到中等水平的 HER2 表达以及无到低水平的 HER2 基因扩增相关。在 17 例 HER2 FISH 结果不确定的患者中，35.3%（6/17）的肿瘤显示 GH。与没有 GH 的 HER2 阳性肿瘤相比，具有 HER2 GH 的肿瘤与较低的组织学分级、较小的肿瘤大小以及倾向于激素受体表达显著相关。HER2 GH 是导致乳腺癌 FISH 检测结果不确定的一个重要原因。具有 HER2 GH 的肿瘤具有与 HER2 阴性肿瘤而非没有 GH 的 HER2 阳性肿瘤更相似的生物学特征。这些发现表明需要指南来阐明是否真正受益于 HER2 靶向治疗的乳腺癌患者中存在 GH。
