Gene Status in HER2 Equivocal Breast Carcinomas: Impact of Distinct Recommendations and Contribution of a Polymerase Chain Reaction-Based Method
Gene Status in HER2 Equivocal Breast Carcinomas: Impact of Distinct Recommendations and Contribution of a Polymerase Chain Reaction-Based Method
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DOI：
10.1634/theoncologist.2014-0195
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发表时间：
2014-11-01
期刊：
影响因子：
5.8
通讯作者：
Marchio, Caterina
中科院分区：
文献类型：
--
作者：
Sapino, Anna;Maletta, Francesca;Marchio, Caterina
背景。这项针对 HER2 表达模棱两可的癌症的研究的主要目的是评估关于通过荧光原位杂交 (FISH) 识别适合使用抗 HER2 药物的患者的不同建议的影响，并阐明多重连接依赖性探针扩增 (MLPA) 是否可以支持评估 HER2 基因状态。方法。通过双色 FISH 对 957 例免疫组织化学评估的 HER2 可疑病例进行了分析。结果根据美国食品药品管理局 (FDA) 和欧洲药品管理局 (EMA) 指南以及美国临床肿瘤学会 (ASCO) 和美国病理学家学会 (CAP) 2007 年和 2013 年双信号和单信号原位杂交 (ISH) 测定指南进行评估。对 112 例病例的亚组进行了 MLPA。结果。 HER2 扩增范围为 15%（ASCO/CAP 2007 HER2/CEP17 比率）至 29.5%（FDA/EMA HER2 拷贝数）。根据ASCO/CAP 2013年对双信号HER2检测的解释，ISH阳性癌占19.7%。与 ASCO/CAP 2007 比率相比，这种方法将所有 32 例病例 (3.34%) 标记为阳性，其中 HER2/CEP17 比率2 以及每个细胞的平均 HER2 拷贝数 >= 6.0 个信号。相比之下，只有 1 例 HER2 拷贝数 = 2 的病例被诊断为阳性。 MLPA 数据与 FISH 结果相关性较差，因为 33.9% 的扩增癌中存在异质 HER2 扩增；然而，MLPA 排除了 75% ISH 评估的 HER2 不确定癌症中的 HER2 扩增。结论。 ASCO/CAP 2013 指南似乎改善了 HER2 阳性癌症的识别。基于聚合酶链式反应的方法（例如 MLPA）可能会有所帮助，前提是 ISH 排除了异质扩增。
Background. The primary objectives of this study on carcinomas with equivocal HER2 expression were to assess the impact of distinct recommendations with regard to identifying patients eligible for anti-HER2 agents by fluorescence in situ hybridization (FISH) and to elucidate whether multiplex ligation-dependent probe amplification (MLPA) may be of support in assessing HER2 gene status.Methods. A cohort of 957 immunohistochemistry-evaluated HER2-equivocal cases was analyzed by dual-color FISH. The results were assessed according to U. S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) guidelines and American Society of Clinical Oncology (ASCO) and College of American Pathologists (CAP) 2007 and 2013 guidelines for dual- and single-signal in situ hybridization (ISH) assays. A subgroup of 112 cases was subjected to MLPA.Results. HER2 amplification varied from15% (ASCO/CAP 2007 HER2/CEP17 ratio) to 29.5% (FDA/EMA HER2 copy number). According to the ASCO/CAP 2013 interpretation of the dual-signal HER2 assay, ISH-positive carcinomas accounted for 19.7%. In contrast with the ASCO/CAP 2007 ratio, this approach labeled as positive all 32 cases (3.34%) with a HER2/CEP17 ratio,2 and an average HER2 copy number >= 6.0 signals per cell. In contrast, only one case showing a HER2 copy number = 2 was diagnosed as positive. MLPA data correlated poorly with FISH results because of the presence of heterogeneous HER2 amplification in 33.9% of all amplified carcinomas; however, MLPA ruled out HER2 amplification in 75% of ISH-evaluated HER2-equivocal carcinomas.Conclusion. The ASCO/CAP 2013 guidelines seem to improve the identification of HER2-positive carcinomas. Polymerase chain reaction-based methods such as MLPA can be of help, provided that heterogeneous amplification has been ruled out by ISH.