Kurosumi Masafumi
Department of Pathology, Saitama Cancer Center, 818 Komuro, Ina-machi, Kitaadachi-gun, Saitama 362-0806, Japan.
Breast Cancer. 2009;16(4):284-7. doi: 10.1007/s12282-009-0159-z. Epub 2009 Aug 6.
Molecular-targeted therapy using trastuzumab, a humanized monoclonal antibody against human epidermal growth factor receptor type-2 (HER-2), is considered to be effective for metastatic as well as primary breast cancer and has already become a worldwide standard therapy for patients with HER-2 protein over-expression and gene amplification. Pretreatment evaluation of HER-2 status is considered to be essential for selection of patients, and according to the generally used algorithm, cases with an immunohistochemistry (IHC) score of 3+ and positivity upon fluorescence in situ hybridization (FISH) are thought to be eligible for trastuzumab therapy. In order to develop an appropriate domestic HER-2 testing system in Japan, the Trastuzumab Pathology Committee was established in 2000 and has been used as a forum for active discussions of policies related to HER-2 testing. After trastuzumab therapy and HER-2 testing had become widely adopted internationally, new guidelines for HER-2 testing were proposed by the ASCO/CAP group in 2007. Since then, these guidelines have gradually become accepted and used in many large-scale clinical studies of HER-2-targeting agents. On the other hand, new ISH methods have been introduced, such as bright-field HER-2 and chromosome 17 centromere double in situ hybridization (BDISH) and dual color-chromogenic in situ hybridization (dc-CISH). These methods make it possible to examine HER-2 gene amplification using only one paraffin section like the dc-FISH method, and to observe grains on the HER-2 gene and centrosome-17 by conventional microscopy. These approaches are considered to be reliable and equally as effective as the dc-FISH method. Accurate evaluation of HER-2 status is thought to be most important for appropriate selection of breast cancer patients who will obtain genuine benefit from trastuzumab treatment. In order to perform effective evaluation of HER-2 status, it is necessary to establish a reliable HER-2 examination system and to maintain its quality at a high level.
曲妥珠单抗是一种针对人表皮生长因子受体2（HER-2）的人源化单克隆抗体，分子靶向治疗被认为对转移性乳腺癌和原发性乳腺癌均有效，并且已经成为HER-2蛋白过表达和基因扩增患者的全球标准治疗方法。HER-2状态的预处理评估被认为是患者选择的关键，根据普遍使用的算法，免疫组织化学（IHC）评分为3+且荧光原位杂交（FISH）呈阳性的病例被认为适合接受曲妥珠单抗治疗。为了在日本开发合适的国内HER-2检测系统，曲妥珠单抗病理委员会于2000年成立，并一直作为积极讨论HER-2检测相关政策的论坛。在曲妥珠单抗治疗和HER-2检测在国际上广泛应用之后，ASCO/CAP小组于2007年提出了新的HER-2检测指南。从那时起，这些指南逐渐被许多HER-2靶向药物的大规模临床研究所接受和使用。另一方面，引入了新的原位杂交（ISH）方法，如明场HER-2和17号染色体着丝粒双原位杂交（BDISH）以及双色显色原位杂交（dc-CISH）。这些方法使得仅使用一张石蜡切片就可以像dc-FISH方法一样检测HER-2基因扩增，并通过传统显微镜观察HER-2基因和17号中心体上的颗粒。这些方法被认为是可靠的，并且与dc-FISH方法同样有效。准确评估HER-2状态被认为对于适当选择将从曲妥珠单抗治疗中真正获益的乳腺癌患者最为重要。为了有效评估HER-2状态，有必要建立可靠的HER-2检测系统并将其质量维持在高水平。
