Nitta Hiroaki, Kelly Brian D, Allred Craig, Jewell Suzan, Banks Peter, Dennis Eslie, Grogan Thomas M
Medical & Scientific Affairs and Technology & Applied Research, Ventana Medical Systems, Inc., Tucson, Arizona, USA.
Technology & Applied Research, Ventana Medical Systems, Inc., Tucson, Arizona, USA.
Pathol Int. 2016 Jun;66(6):313-24. doi: 10.1111/pin.12407. Epub 2016 Apr 7.
Humanized monoclonal anti-human growth factor receptor 2 (HER2) antibody trastuzumab was approved for HER2 positive breast cancer patient treatment 11 years after the demonstration of HER2 gene amplification associated with the HER2 protein overexpression in breast cancer in 1987. HER2 positive status of breast cancer patients is assessed by HER2 gene amplification with in situ hybridization (ISH) and/or HER2 protein overexpression with immunohistochemistry (IHC). Because the discordance between quantitative HER2 ISH and subjective, semi-quantitative HER2 IHC assay results is a well-recognized issue of HER2 testing, we developed an assay combining HER2 ISH and HER2 IHC assays (HER2 gene-protein assay; HER2 GPA) as one test on the same tissue section. HER2 GPA allows pathologists to score the HER2 gene and HER2 protein status simultaneously at the individual cell level. The possibility that HER2 GPA may become the next generation of HER2 testing is discussed, particularly for cases in which it is difficult to assess the HER2 status of breast cancer patients due to the HER2 heterogeneity.
1987年证实乳腺癌中HER2基因扩增与HER2蛋白过表达相关，11年后，人源化抗人表皮生长因子受体2（HER2）单克隆抗体曲妥珠单抗被批准用于HER2阳性乳腺癌患者的治疗。乳腺癌患者的HER2阳性状态通过原位杂交（ISH）检测HER2基因扩增和/或免疫组织化学（IHC）检测HER2蛋白过表达来评估。由于定量HER2 ISH与主观、半定量HER2 IHC检测结果之间的不一致是HER2检测中一个公认的问题，我们开发了一种将HER2 ISH和HER2 IHC检测相结合的检测方法（HER2基因-蛋白检测；HER2 GPA），在同一组织切片上作为一项检测。HER2 GPA使病理学家能够在单个细胞水平上同时对HER2基因和HER2蛋白状态进行评分。本文讨论了HER2 GPA成为下一代HER2检测方法的可能性，特别是对于因HER2异质性而难以评估乳腺癌患者HER2状态的病例。
