Department of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
J Clin Oncol. 2010 Jul 10;28(20):3264-70. doi: 10.1200/JCO.2009.25.9366. Epub 2010 May 24.
Core needle biopsies (CNBs) are widely used to determine human epidermal growth factor receptor 2 (HER2) status in breast cancer. Recent publications reported up to 20% false-positive results on CNBs if immunohistochemistry (IHC) is compared with fluorescent in situ hybridization (FISH). To clarify, if confirmation of IHC positivity by FISH is generally required, we analyzed the reliability of IHC positivity on CNBs versus surgical specimens in a multi-institutional study.
Five pathologic laboratories contributed to this study by performing IHC on 500 CNBs and the corresponding surgical specimens overall. If IHC revealed score 2+ or 3+, HER2 status was confirmed by FISH in a central laboratory. We compared evaluation according to US Food and Drug Administration-approved scoring criteria and recently published American Society of Clinical Oncology (ASCO)-College of American Pathologists (CAP) guidelines.
CNBs scored 3+ revealed five false-positive results if scoring followed the US Food and Drug Administration criteria (five of 40; 12.5%) and two false-positives in terms of the ASCO-CAP criteria (two of 33; 6.1%). IHC was false negative in one CNB only. By contrast, IHC on surgical specimens revealed five false-negative results, but only one false-positive result (one of 35; 2.9%) if scored following US Food and Drug Administration-approved criteria. With the aid of the ASCO-CAP criteria, false-positive IHC results were obtained in only one of the five participating institutions.
IHC 3+ scores on CNBs proved to be reliable in four of the five participating institutions if scoring followed the ASCO-CAP criteria. Therefore, accurate determination of HER2 status in breast cancer is possible on CNB using the common strategy to screen all cases by IHC and retest only 2+ scores by FISH. Prerequisites are quality assurance and the application of the new ASCO-CAP criteria.
核心针活检（CNB）广泛用于确定乳腺癌的人类表皮生长因子受体 2（HER2）状态。如果将免疫组织化学（IHC）与荧光原位杂交（FISH）进行比较，最近的出版物报告了高达 20%的 CNB 假阳性结果。为了澄清，如果普遍需要通过 FISH 确认 IHC 阳性，则我们在多机构研究中分析了 CNB 与手术标本上的 IHC 阳性的可靠性。
五个病理实验室通过对总共 500 个 CNB 和相应的手术标本进行 IHC 分析参与了这项研究。如果 IHC 显示评分 2+或 3+，则在中央实验室通过 FISH 确认 HER2 状态。我们根据美国食品和药物管理局批准的评分标准和最近发布的美国临床肿瘤学会（ASCO）-美国病理学家协会（CAP）指南进行了评估比较。
根据美国食品和药物管理局的标准评分，CNB 的 3+评分显示有五个假阳性结果（五分之四十；12.5%），而根据 ASCO-CAP 标准有两个假阳性结果（三十三分之二；6.1%）。只有一个 CNB 的 IHC 为假阴性。相比之下，如果按照美国食品和药物管理局批准的标准评分，手术标本的 IHC 显示有五个假阴性结果，但只有一个假阳性结果（三十五分之一；2.9%）。借助 ASCO-CAP 标准，五个参与机构中只有一个获得了假阳性 IHC 结果。
如果按照 ASCO-CAP 标准评分，五个参与机构中的四个机构的 CNB 的 IHC 3+评分被证明是可靠的。因此，使用通过 IHC 筛选所有病例并仅通过 FISH 重新测试 2+评分的常见策略，在 CNB 上可以准确确定乳腺癌的 HER2 状态。前提是质量保证和新的 ASCO-CAP 标准的应用。
