Department of Pathology, Massachusetts General Hospital, Boston, MA, 02114, USA.
Harvard Medical School, USA.
Hum Pathol. 2022 Sep;127:50-55. doi: 10.1016/j.humpath.2022.05.019. Epub 2022 Jun 4.
Breast cancers are currently eligible for treatment with anti-HER2 therapies if they exhibit amplification of the gene ERBB2 and overexpression of its protein product HER2. Recently, breast cancers with low HER2 expression have shown response to novel anti-HER2 antibody-drug conjugates, and the lower end of "low-HER2" tumors has not yet been clinically delineated. The historically binary approach to HER2 scoring will need to evolve and reporting of HER2 status may require refinement to better stratify low-HER2 statuses. We performed a quality review of HER2 immunohistochemical (IHC) scoring of breast carcinomas with low HER2 expression (71 core biopsies and 51 excisions). We also investigated the feasibility of discerning cases with total lack of HER2 expression from those cases with "very low" HER2 expression that did not meet current criteria for a HER2(1+) score. Rescoring HER2 achieved substantial agreement when performed at 200×, and near-perfect agreement at 400× magnification. Examination under 400× magnification led to recognition of more cases with HER2 expression. Less than 10% of cases showed complete lack of HER2 protein expression by IHC. Cases with "very low" expression were readily identified, and such a category would be feasible to implement in pathologist workflow.
如果乳腺癌的基因 ERBB2 扩增和其蛋白产物 HER2 过度表达，则目前有抗 HER2 治疗方法可用于治疗。最近，HER2 低表达的乳腺癌对新型抗 HER2 抗体药物偶联物有反应，而“低 HER2”肿瘤的低端尚未在临床上划定。HER2 评分的历史二分法方法需要发展，HER2 状态的报告可能需要改进，以更好地分层低 HER2 状态。我们对 HER2 免疫组化（IHC）评分低的乳腺癌（71 例核心活检和 51 例切除术）进行了质量审查。我们还研究了从那些不符合当前 HER2(1+)评分标准的“非常低”HER2 表达的病例中辨别出完全缺乏 HER2 表达的病例的可行性。在 200×放大倍数下重新评分时，HER2 达到了实质性的一致性，在 400×放大倍数下达到了近乎完美的一致性。在 400×放大倍数下检查，识别出更多具有 HER2 表达的病例。不到 10%的病例通过 IHC 显示完全缺乏 HER2 蛋白表达。很容易识别出“非常低”表达的病例，这种分类在病理学家的工作流程中是可行的。
