Department of Pathology and Laboratory Medicine, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan Er Lu, Guangzhou, 510080, China.
Department of Breast Cancer, Cancer Center, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
Breast Cancer Res Treat. 2017 Dec;166(3):757-764. doi: 10.1007/s10549-017-4479-y. Epub 2017 Aug 31.
The updated 2013 American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 (HER2) testing have made some major changes in HER2 fluorescence in situ hybridization (FISH) interpretation criteria with additional FISH equivocal cases. Repeat HER2 testing is recommended after initial HER2 FISH equivocal results; however, little is known about its impact on final HER2 status. The aim of this study is to investigate whether reflex test clarifies HER2 status, and to characterize clinicopathological features of the newly defined HER2 equivocal group.
A total of 886 consecutive cases of primary invasive breast cancer conducted with dual-probe HER2 FISH testing between November 2013 and December 2015 were reviewed. HER2 immunohistochemistry (IHC) and FISH testing were performed on a different tissue block or a new specimen after initial HER2 FISH equivocal results.
Compared to 2007 guideline, 85 (9.6%) cases changed their category by using 2013 guideline. The major change of the 85 cases is that 57 (6.4%) cases in HER2 FISH-negative category changed to equivocal, and the equivocal category cases increased from 36 to 67. HER2 FISH equivocal was significantly associated with HER2 IHC equivocal (2+) and chromosome 17 polysomy (P < 0.01). Repeat testing by IHC and FISH clarified HER2 status in 33 and 42% of HER2 equivocal cases, respectively. Overall 32 (48%) initial HER2 equivocal cases stayed HER2 equivocal after repeat FISH and or IHC testing. These tumors were ER/PR+, with high KI-67 index.
New guidelines classify more HER2 FISH equivocal cases. Repeat HER2 testing clarifies HER2 status in about 50% of initial HER2 FISH equivocal cases. In addition, HER2 equivocal cases merit further study as there is limited information about prognosis and optimal treatment strategy for this population.
美国临床肿瘤学会/美国病理学家学院（ASCO/CAP）更新的 2013 年人表皮生长因子受体 2（HER2）检测指南建议对 HER2 荧光原位杂交（FISH）检测的解释标准进行了一些重大修改，增加了 FISH 结果不确定的病例。建议对初始 HER2 FISH 结果不确定的病例进行重复 HER2 检测；然而，对于其对最终 HER2 状态的影响知之甚少。本研究旨在探讨反射性检测是否能明确 HER2 状态，并分析新定义的 HER2 不确定组的临床病理特征。
回顾了 2013 年 11 月至 2015 年 12 月期间进行的 886 例连续原发性浸润性乳腺癌的双探针 HER2 FISH 检测结果。在初始 HER2 FISH 结果不确定后，对免疫组织化学（IHC）和 FISH 检测使用不同的组织块或新标本进行。
与 2007 年指南相比，85 例（9.6%）病例根据 2013 年指南改变了分类。85 例病例的主要变化是，HER2 FISH 阴性组中有 57 例（6.4%）病例变为不确定，不确定组病例从 36 例增加到 67 例。HER2 FISH 不确定与 HER2 IHC 不确定（2+）和 17 号染色体多倍体显著相关（P<0.01）。在 HER2 不确定病例中，IHC 和 FISH 重复检测分别使 33%和 42%的病例明确了 HER2 状态。总体而言，32 例（48%）初始 HER2 不确定病例在重复 FISH 和/或 IHC 检测后仍为 HER2 不确定。这些肿瘤为 ER/PR+，具有较高的 KI-67 指数。
新指南将更多的 HER2 FISH 不确定病例归类。约 50%的初始 HER2 FISH 不确定病例通过重复 HER2 检测明确了 HER2 状态。此外，由于对此人群的预后和最佳治疗策略信息有限，HER2 不确定病例值得进一步研究。
