Department of Pathology, Academic Medical Center, Meibergdreef 9, Amsterdam, 1100 DD, The Netherlands.
Breast Cancer Res. 2012 Jun 13;14(3):R93. doi: 10.1186/bcr3208.
Overexpression of the human epidermal growth factor receptor 2 (HER2) as a result of HER2 gene amplification is associated with a relatively poor prognosis in breast cancer and is predictive of HER2-targeting therapy response. False-positive rates of up to 20% for HER2 testing have been described. HER2-testing laboratories are therefore encouraged to participate in external quality control schemes in order to improve HER2-testing standardization.
This study investigated the feasibility of retesting large numbers of invasive breast cancers for HER2 status on tissue micro-array (TMA) as part of a quality control scheme. For this assessment different HER2 testing methods were used including HER2 detecting antibodies SP3, 4B5, Herceptest and mono color silver in situ hybridization (SISH) and dual color SISH. Final HER2 status for each tumor on the TMA was compared to the local testing result for the same tumor. Discordances between these two results were investigated further by staining whole tumor sections.
For this study, 1,210 invasive breast carcinomas of patients treated in six hospitals between 2006 and 2008 were evaluated. Results from the three immunohistochemistry (IHC) and two in situ hybridization (ISH) assays performed on the TMAs were compared. The final HER2 status on TMA was determined with SP3, 4B5 and mono color SISH. Concordance between local HER2 test results and TMA retesting was 98.0%. Discordant results between local and TMA retesting were found in 20 tumors (2.0%). False positive HER2 IHC results were identified in 13 (1.3%) tumors; false negative IHC results in seven (0.7%) tumors.
Retesting large volumes of HER2 classified breast carcinomas was found to be feasible and can be reliably performed by staining TMAs with SP3, 4B5 and mono color SISH in combination with full-sized slides for discordant cases. The frequency of false-positive results was lower than previously reported in the literature. This method is now offered to other HER2-testing laboratories.
由于 HER2 基因扩增导致的人表皮生长因子受体 2（HER2）过表达与乳腺癌的预后较差相关，并且可预测针对 HER2 的靶向治疗反应。HER2 检测的假阳性率高达 20%。因此，鼓励 HER2 检测实验室参加外部质量控制计划，以提高 HER2 检测的标准化。
本研究调查了在组织微阵列（TMA）上重新测试大量浸润性乳腺癌 HER2 状态的可行性，作为质量控制计划的一部分。为此评估，使用了不同的 HER2 检测方法，包括 HER2 检测抗体 SP3、4B5、Herceptest 和单染原位杂交（SISH）和双染 SISH。TMA 上每个肿瘤的最终 HER2 状态与同一肿瘤的局部检测结果进行比较。进一步通过对整个肿瘤切片进行染色来研究这两个结果之间的差异。
在这项研究中，评估了 2006 年至 2008 年间在六家医院治疗的 1,210 例浸润性乳腺癌患者。比较了在 TMA 上进行的三种免疫组织化学（IHC）和两种原位杂交（ISH）检测的结果。使用 SP3、4B5 和单染 SISH 确定 TMA 上的最终 HER2 状态。局部 HER2 检测结果与 TMA 重新检测的一致性为 98.0%。局部和 TMA 重新检测之间存在 20 个（2.0%）肿瘤的不一致结果。在 13 个（1.3%）肿瘤中发现了假阳性 HER2 IHC 结果；在 7 个（0.7%）肿瘤中发现了假阴性 IHC 结果。
重新检测大量 HER2 分类的乳腺癌被发现是可行的，可以通过用 SP3、4B5 和单染 SISH 染色 TMA 并结合全尺寸幻灯片对不一致的病例进行可靠地检测。假阳性结果的频率低于文献中先前报道的频率。该方法现已提供给其他 HER2 检测实验室。
