Current issues in ER and HER2 testing by IHC in breast cancer
Current issues in ER and HER2 testing by IHC in breast cancer
复制标题
DOI：
10.1038/modpathol.2008.34
复制
发表时间：
2008-05-01
期刊：
影响因子：
7.5
通讯作者：
Gown, Allen M.
中科院分区：
文献类型：
--
作者：
Gown, Allen M.
雌激素受体（ER）的存在，如通过免疫组织化学（IHC）检测，是乳腺癌临床结果的弱预后标志物，但对例如基于他莫昔芬的治疗的反应是强预测标志物。与所有IHC标记物一样，组织固定（类型和持续时间）、抗体选择和阳性免疫染色判读阈值等因素会显著影响检测准确性和重现性。例如，用于检测ER的最佳固定需要在福尔马林中至少6-8小时，并且使用较新的抗体如SP1可以识别可能受益于激素治疗的其他患者。尽管阳性阈值可能低至1%的肿瘤细胞显示核信号，但最近的研究似乎证明了ER IHC的二分法，绝大多数病例显示全部阳性或全部阴性结果。这可能有助于决定激素治疗的适当性，但通过IHC或其他方法定量ER可能在未来发挥更重要的作用。具有人表皮受体蛋白-2（c-erbB-2; HER 2）改变的乳腺癌的识别至关重要，因为此类肿瘤需要独特的治疗，包括使用靶向治疗，如曲妥珠单抗。HER 2在DNA（扩增）和蛋白质（过表达）水平上的改变通常同时发生，荧光原位杂交（FISH）或IHC都是评估这些改变的准确方法。然而，最近的研究表明，在FISH和IHC HER 2研究中存在严重的再现性问题。为了解决这个问题，美国临床肿瘤学家协会和美国病理学家学院的联合委员会颁布了HER 2检测的新指南。其中包括：（a）建议组织固定超过6小时且少于48小时;（B）新的评分标准，包括用于3+分类的30%强免疫染色的新阈值;（c）引入术语“不确定”以表征通过IHC为2+和/或通过FISH显示HER 2/17染色体比率在1.8和2.2之间的HER 2研究;（d）要求实验室验证HER 2检测方法，一般是通过与另一种HER 2方法交叉检测病例，实验室必须在阳性和阴性检测中达到95%的一致性;
The presence of estrogen receptors (ERs), as detected by immunohistochemistry (IHC), is a weak prognostic marker of clinical outcome in breast cancer, but a strong predictive marker for response, for example, to tamoxifen-based therapy. As with all IHC markers, factors such as tissue fixation ( both type and duration), the choice of antibody, and the threshold for interpretation of positive immunostaining can dramatically affect test accuracy and reproducibility. For example, optimal fixation for detection of ER requires at least 6-8 h in formalin, and the use of newer antibodies such as SP1 may identify additional patients who might benefit from hormonal therapy. Although the threshold for positivity may be as few as 1% of tumor cells showing nuclear signal, recent studies appear to demonstrate a dichotomization of ER IHC, with the vast majority of cases showing all positive or all negative results. This may be helpful in dictating the appropriateness of hormonal therapy, but quantification of ER by IHC, or other methods, may play a more important role in the future. Breast cancers with human epidermal receptor protein-2 (c-erbB-2; HER2) alterations are critical to identify because such tumors require unique treatment, including the use of targeted therapies such as trastuzumab. HER2 alterations at the DNA ( amplification) and protein ( overexpression) level usually occur in concert, and both fluorescence in situ hybridization ( FISH) or IHC can be accurate methods to assess these alterations. However, recent studies have suggested that serious reproducibility issues exist in both FISH and IHC HER2 studies. To address this, a joint committee of both the American Society for Clinical Oncologists and the College of American Pathologists has promulgated new guidelines for HER2 testing. These include the following: ( a) recommendations for tissue fixation for more than 6 and less than 48 h; (b) new scoring criteria, including a new threshold of 30% strong immunostaining for classification of 3+; ( c) introduction of the term 'equivocal' to characterize HER2 studies that are 2+ by IHC and/or show HER2/chromosome 17 ratios of between 1.8 and 2.2 by FISH; (d) requirements for laboratories to validate HER2 assays, generally through the cross-testing of cases with another HER2 methodology, with laboratories required to attain 95% concordance for both positive and negative tests; ( e) participation in HER2 proficiency testing.