Naval Medical Center San Diego, San Diego, CA, USA.
Department of Pathology, Division of Women's and Perinatal Pathology, Brigham and Women's Hospital, Boston, MA, USA.
Mod Pathol. 2021 Mar;34(3):603-612. doi: 10.1038/s41379-020-00695-5. Epub 2020 Oct 19.
Uterine serous carcinoma is an aggressive subtype of endometrial cancer that accounts for fewer than 10% of endometrial carcinomas but is responsible for about half of deaths. A subset of cases has HER2 overexpression secondary to ERBB2 gene amplification, and these patients may benefit from anti-HER2 therapies, such as trastuzumab. HER2 protein overexpression is currently assessed by immunohistochemistry (IHC) and ERBB2 gene amplification by fluorescence in situ hybridization (FISH). Targeted next-generation sequencing (NGS) is increasingly used to routinely identify predictive and prognostic molecular abnormalities in endometrial carcinoma. To investigate the ability of a targeted NGS panel to detect ERBB2 amplification, we identified cases of uterine serous carcinoma (n = 93) and compared HER2 expression by IHC and copy number assessed by FISH with copy number status assessed by NGS. ERBB2 copy number status using a combination of IHC and FISH was interpreted using the 2018 ASCO/CAP guidelines for breast carcinoma. ERBB2 amplification by NGS was determined by the relative number of reads mapping to ERBB2 in tumor DNA compared to control nonneoplastic DNA. Cases with copy number ≥6 were considered amplified and copy number <6 were non-amplified. By IHC, 70 specimens were classified as negative (0 or 1+), 19 were classified as equivocal (2+), and 4 were classified as positive (3+). Using combined IHC/FISH, ERBB2 amplification was observed in 8 of 93 cases (9%). NGS identified the same 8 cases with copy number ≥6; all 85 others had copy number <6. In this series, NGS had 100% concordance with combined IHC/FISH in identifying ERBB2 amplification. NGS is highly accurate in detecting ERBB2 amplification in uterine serous carcinoma and provides an alternative to measurement by IHC and FISH.
子宫浆液性癌是一种侵袭性子宫内膜癌亚型，占子宫内膜癌的比例不到 10%，但导致了大约一半的死亡病例。一部分病例存在 HER2 过表达，这是由于 ERBB2 基因扩增所致，这些患者可能受益于抗 HER2 治疗，如曲妥珠单抗。HER2 蛋白过表达目前通过免疫组织化学（IHC）评估，ERBB2 基因扩增通过荧光原位杂交（FISH）评估。靶向下一代测序（NGS）越来越多地用于常规识别子宫内膜癌中的预测性和预后性分子异常。为了研究靶向 NGS 面板检测 ERBB2 扩增的能力，我们鉴定了子宫浆液性癌病例（n=93），并比较了 IHC 评估的 HER2 表达和 FISH 评估的拷贝数与 NGS 评估的拷贝数状态。使用 2018 年 ASCO/CAP 乳腺癌指南解读 IHC 和 FISH 组合的 ERBB2 拷贝数状态。NGS 检测到的 ERBB2 扩增通过肿瘤 DNA 中与对照非肿瘤 DNA 相比映射到 ERBB2 的相对读数数来确定。拷贝数≥6 的病例被认为是扩增的，拷贝数<6 的病例是非扩增的。通过 IHC，70 个标本被归类为阴性（0 或 1+），19 个标本归类为不确定（2+），4 个标本归类为阳性（3+）。使用联合 IHC/FISH，在 93 例病例中观察到 8 例 ERBB2 扩增（9%）。NGS 鉴定出了相同的 8 例拷贝数≥6 的病例；其他 85 例的拷贝数均<6。在该系列中，NGS 在识别 ERBB2 扩增方面与联合 IHC/FISH 具有 100%的一致性。NGS 在检测子宫浆液性癌中的 ERBB2 扩增方面非常准确，并提供了替代 IHC 和 FISH 的方法。
