Department of Medicine, Dalhousie University, Halifax, NS, Canada.
Department of Pathology and Laboratory Medicine, Dalhousie University, Halifax, NS, Canada; Nova Scotia Health Authority, Halifax, NS, Canada.
Ann Diagn Pathol. 2022 Aug;59:151953. doi: 10.1016/j.anndiagpath.2022.151953. Epub 2022 Apr 21.
Current guidelines recommend HER2 testing on all primary invasive breast cancers and re-biopsy at disease relapse. The discordance rate between HER2-negative primaries and HER2 IHC2+ metastases that are ISH-amplified is unknown. We hypothesize that the majority of such cases are non-amplified. ISH testing is time-consuming and resource-intensive, and there may be situations where it is unnecessary. A retrospective review of IHC2+ metastatic lesions assessed with ISH at our center from 2013 to 2021 was undertaken. 105 cases were identified after exclusion of cases missing HER2 results, with primaries of unconfirmed origin, and cases of synchronous primary and metastatic disease. IHC and ISH results were recorded with detailed slide review of discordant cases. 91/105 metastases had HER2-negative primaries (87%). A metastasis was significantly more likely to be HER2-negative when the primary was HER2-negative (93%) versus positive (43%) (p < 0.0001). 54/91 primaries were IHC2+/ISH-non-amplified, and 50/54 (93%) corresponding metastases had identical results. Of the 37 HER2-negative primaries that were IHC0/1+, 35 (95%) corresponding metastases were ISH-non-amplified. Six metastases in cases with HER2-negative primaries were discordant. Characteristics of metastases suggesting ISH testing was warranted to assess for discordance included IHC heterogeneity, morphological discordance, increased staining of moderate intensity, and ER/PR discordance. One or more of these factors were present in all discordant metastases. Our results suggest selective ISH testing on HER2 IHC2+ breast cancer metastases in the context of HER2-negative primary disease may be appropriate when there is careful review of the IHC. Validation of our findings awaits further studies with larger sample sizes.
目前的指南建议对所有原发性浸润性乳腺癌进行 HER2 检测，并在疾病复发时进行重新活检。HER2 阴性原发性肿瘤与 HER2 IHC2+转移灶中存在 ISH 扩增的不一致率尚不清楚。我们假设大多数此类病例都是非扩增的。ISH 检测既费时又费资源，而且可能存在不必要的情况。我们对 2013 年至 2021 年在我们中心进行 ISH 评估的 HER2 IHC2+转移性病变进行了回顾性审查。排除了 HER2 结果缺失、原发灶来源不明、同时存在原发性和转移性疾病的病例后，共鉴定出 105 例病例。记录了 IHC 和 ISH 结果，并对不一致的病例进行了详细的切片审查。在 105 例转移灶中，91 例（87%）的原发灶为 HER2 阴性。当原发灶为 HER2 阴性时，转移灶更有可能为 HER2 阴性（93%）而非阳性（43%）（p<0.0001）。在 91 例 HER2 阴性的原发性肿瘤中，54 例（93%）为 IHC2+/ISH-非扩增，且 54 例（93%）对应的转移灶具有相同的结果。在 37 例 HER2 阴性的 IHC0/1+原发性肿瘤中，35 例（95%）对应的转移灶为 ISH-非扩增。在 HER2 阴性原发性肿瘤的 6 例转移灶中存在不一致。提示需要进行 ISH 检测以评估不一致性的转移灶特征包括 IHC 异质性、形态学不一致、中度强度染色增加以及 ER/PR 不一致。所有不一致的转移灶均存在这些因素中的一个或多个。我们的结果表明，在 HER2 阴性原发性疾病背景下，对 HER2 IHC2+乳腺癌转移灶进行选择性 ISH 检测可能是合适的，同时需要仔细审查 IHC。需要进一步的研究来验证我们的发现，并扩大样本量。
