Burandt E, Sauter G
Institut für Pathologie, Universitätsklinikum Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg.
Pathologe. 2010 Oct;31 Suppl 2:285-91. doi: 10.1007/s00292-010-1348-4.
The HER2 gene is amplified and overexpressed in about 15%-20% of breast cancers. For every newly diagnosed breast cancer HER2 testing is a standard routine procedure. This article focuses on a number of issues raised in the context of current HER2 testing in breast cancer. It particularly points out issues arising in the recently published ASCO-CAP (American Society of Clinical Oncology/College of American Pathologists) guideline recommendations for clinical testing of HER2. Despite the significant correlation between HER2 status determination by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), standard considerations of laboratory testing, such as test accuracy, reproducibility and precision as well as current data, favor FISH methods over IHC assay methods for the determination of HER2 status. Biological and technical considerations of HER2 testing are also important in clinical practice. For example, HER2 gene amplification is directly linked to the protein expression level in breast cancer; however, the HER2 protein is not consistently analyzed on formalin fixed tissues due to variability in fixation methods/times and the impact of this fixation on HER2 protein antigenicity. FISH is significantly less dependent on tissue fixation artifacts. Hence, FISH is more reproducible between both central and peripheral laboratories than IHC and is more accurate for HER2 measurement, as well as being more strongly correlated with responsiveness to trastuzumab and lapatinib treatment. Until other methods are able to ensure similar test accuracy, reproducibility, precision and predictive value, FISH is recommended as the primary HER2 testing modality for women with breast cancer who are candidates for HER2-targeted therapies.
HER2基因在约15%-20%的乳腺癌中存在扩增和过表达。对于每一例新诊断的乳腺癌，HER2检测都是标准的常规程序。本文重点关注当前乳腺癌HER2检测背景下出现的一些问题。它特别指出了最近发布的美国临床肿瘤学会/美国病理学家学会（ASCO-CAP）HER2临床检测指南建议中出现的问题。尽管免疫组织化学（IHC）和荧光原位杂交（FISH）检测HER2状态之间存在显著相关性，但实验室检测的标准考量因素，如检测准确性、可重复性和精密度以及当前数据，在确定HER2状态方面更倾向于FISH方法而非IHC检测方法。HER2检测的生物学和技术考量在临床实践中也很重要。例如，HER2基因扩增与乳腺癌中的蛋白表达水平直接相关；然而，由于固定方法/时间的差异以及这种固定对HER2蛋白抗原性的影响，在福尔马林固定组织上对HER2蛋白的分析并不一致。FISH对组织固定假象的依赖性显著降低。因此，与IHC相比，FISH在中心实验室和外周实验室之间更具可重复性，对HER2测量更准确，并且与曲妥珠单抗和拉帕替尼治疗的反应性相关性更强。在其他方法能够确保类似的检测准确性、可重复性、精密度和预测价值之前，对于适合HER2靶向治疗的乳腺癌女性，建议将FISH作为主要的HER2检测方式。
