From the Department of Pathology, Yale University, New Haven, Connecticut.
Arch Pathol Lab Med. 2022 Jun 10;146(5):0. doi: 10.5858/arpa.2021-0547-OA.
CONTEXT.—: Targeted anti-human epidermal growth factor receptor 2 (HER2) therapy has recently become the standard for advanced-stage and recurrent HER2-positive endometrial serous carcinoma (ESC) in the United States, and an endometrial carcinoma-specific HER2 testing algorithm has been proposed. However, comprehensive studies on the specific features of HER2 gene amplification in these tumors are lacking.
OBJECTIVE.—: To evaluate the characteristics of HER2 amplification in ESC in the context of breast and gastric HER2 fluorescence in situ hybridization (FISH) guidelines.
DESIGN.—: Ninety-four ESCs with available HER2 immunohistochemistry (IHC) and FISH were included. HER2 IHC was scored according to the proposed endometrial carcinoma-specific algorithm and FISH was evaluated by using the 2018 ESC clinical trial criteria, the American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) 2016 gastric criteria, and ASCO/CAP 2013 and 2018 breast criteria.
RESULTS.—: Most tumors (90.4%; 85 of 94) had a 2+ HER2 IHC score. Polysomy of chromosome 17 was present in 16% (15 of 94) and monosomy 17 was seen in 2% (2 of 94) of tumors. HER2 FISH interpretation per the clinical trial criteria (HER2/CEP17 ratio ≥ 2.0) showed 99% concordance with the current gastric and breast HER2 FISH interpretations.
CONCLUSIONS.—: Our results support the clinical trial criteria for HER2 FISH in ESC with a modification to include HER2 IHC 2+ and HER2/CEP17 ratio less than 2.0 and average HER2 copy number of 6.0 or greater in the HER2-positive category. Future prospective clinical investigations are necessary to assess the correlation between specific HER2 FISH result categories and therapeutic response.
针对人表皮生长因子受体 2（HER2）的靶向治疗最近已成为美国晚期和复发性 HER2 阳性子宫内膜浆液性癌（ESC）的标准治疗方法，并且已经提出了一种子宫内膜癌特异性的 HER2 检测算法。然而，对于这些肿瘤中 HER2 基因扩增的具体特征，尚无全面的研究。
根据乳腺癌和胃癌 HER2 荧光原位杂交（FISH）指南，评估 ESC 中 HER2 扩增的特征。
纳入了 94 例具有可用的 HER2 免疫组化（IHC）和 FISH 的 ESC。HER2 IHC 根据提出的子宫内膜癌特异性算法进行评分，FISH 根据 2018 年 ESC 临床试验标准、美国临床肿瘤学会/美国病理学家协会（ASCO/CAP）2016 年胃癌标准、ASCO/CAP 2013 年和 2018 年乳腺癌标准进行评估。
大多数肿瘤（90.4%；94 例中有 85 例）HER2 IHC 评分 2+。16%（94 例中有 15 例）的肿瘤存在染色体 17 三体，2%（94 例中有 2 例）的肿瘤存在 17 单体。根据临床试验标准（HER2/CEP17 比值≥2.0）进行 HER2 FISH 解读，与当前胃癌和乳腺癌 HER2 FISH 解读具有 99%的一致性。
我们的结果支持 ESC 中 HER2 FISH 的临床试验标准，对其进行了修改，包括将 HER2 IHC 2+和 HER2/CEP17 比值小于 2.0以及 HER2 阳性类别中平均 HER2 拷贝数为 6.0 或更高纳入其中。需要进行未来的前瞻性临床研究，以评估特定 HER2 FISH 结果类别与治疗反应之间的相关性。
