Department of Medical Sciences, University of Turin Turin, Italy.
Front Oncol. 2013 May 21;3:129. doi: 10.3389/fonc.2013.00129. eCollection 2013.
HER2 overexpression and anti-HER2 agents represent probably the best story of success of individualized therapy in breast cancer. Due to the important therapeutic implications, the issue under the spotlight has been, since ever, the correct identification of true HER2 positivity on tissue specimens. Eligibility to anti-HER2 agents is strictly dependent on the demonstration of HER2 overexpression (by immunohistochemistry) or of HER2 gene amplification by in situ techniques (fluorescence in situ hybridization, FISH), however there are controversial issues involving cases with "equivocal" HER2 status based on conventional techniques (about 20% of specimens). In terms of HER2 expression a major debate is the presence of full-length and truncated forms of the protein and controversial clinical data have been reported on the therapeutic implications of these HER2 fragments. In terms of HER2 gene assessment, the occurrence of amplification of the chromosome 17 centromeric region (CEP17) has been proven responsible for misleading HER2 FISH results, precluding anti-HER2 based therapy to some patients. Finally HER2 activating mutations have been recently described as a biological mechanisms alternative to HER2 gene amplification. In this review we will focus on the controversies that pathologists and oncologists routinely face in the attempt to design the most tailored treatment for breast cancer patients. We will focus on the HER2 gene and on the protein, both at technical and interpretational levels.
HER2 过表达和抗 HER2 药物代表了乳腺癌个体化治疗最成功的范例。由于其具有重要的治疗意义，因此，组织标本中真正的 HER2 阳性的正确识别一直是备受关注的问题。抗 HER2 药物的使用资格严格取决于 HER2 过表达（免疫组化）或 HER2 基因扩增（原位技术，荧光原位杂交，FISH）的证明，然而，涉及基于常规技术的“不确定”HER2 状态的病例存在争议（约 20%的标本）。在 HER2 表达方面，一个主要的争论是存在全长和截断形式的蛋白质，并且关于这些 HER2 片段的治疗意义的有争议的临床数据已经报道。在 HER2 基因评估方面，已经证明 17 号染色体着丝粒区域（CEP17）的扩增发生是导致误导性 HER2 FISH 结果的原因，从而使一些患者无法接受基于抗 HER2 的治疗。最后，最近描述了 HER2 激活突变作为替代 HER2 基因扩增的生物学机制。在这篇综述中，我们将重点介绍病理学家和肿瘤学家在尝试为乳腺癌患者设计最适合的治疗方案时经常面临的争议。我们将重点关注 HER2 基因和蛋白，从技术和解释层面进行讨论。
