Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
Department of Pathology, Heping Fuyou Branch, Taipei City Hospital, Taipei, Taiwan.
Histopathology. 2021 Nov;79(5):758-767. doi: 10.1111/his.14419. Epub 2021 Aug 6.
The aim of this study was to evaluate human epidermal growth factor receptor 2 (HER2) immunohistochemistry (IHC) in ovarian clear cell carcinoma (OCCC) by using two antibodies and two scoring guidelines in correlation with HER2 amplification and clinicopathological features.
A tissue microarray was constructed by use of a total of 71 OCCC cases for IHC (the A0485 antibody and the 4B5 antibody) and dual-colour silver in-situ hybridisation (DISH). Two pathologists independently scored the IHC according to the 2018 American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) breast cancer guidelines (breast guidelines) and the 2016 ASCO/CAP gastro-oesophageal adenocarcinoma guidelines (gastric guidelines). IHC concordances between A0485 and 4B5 were 87.3-93.0%. Three to 16 (4.2-22.5%) cases had an IHC score of 2+/3+ with frequent basolateral/lateral membranous staining. The 4B5 antibody yielded fewer IHC 2+ cases than the A0485 antibody (n = 2-6 versus n = 5-12). Five (7.0%) cases had HER2 amplification as determined with DISH. Cases with papillary-predominant growth patterns were significantly more likely to have HER2 amplification (P = 0.0051). In predicting DISH results, IHC scored according to the gastric guidelines yielded 100%/100% sensitivity and 83.3-95.5%/98.2-100% specificity, and IHC scored according to the breast guidelines yielded 60-80%/33.3-66.7% sensitivity and 95.5-100%/100% specificity (including/excluding IHC 2+ cases). One case had intratumoral heterogeneity, with discordant results between primary and metastatic tumour specimens.
We demonstrated HER2 amplification in 7% of OCCC cases, and the molecular change is significantly associated with papillary-predominant growth patterns. In predicting HER2 amplification, a combination of 4B5 IHC and gastric guidelines provides the best sensitivity and fewer equivocal (IHC 2+) cases. Given the intratumoral heterogeneity, assessment of HER2 status on whole tissue sections and on both primary and metastatic tumour specimens is recommended.
本研究旨在通过使用两种抗体和两种评分标准，评估卵巢透明细胞癌（OCCC）中人类表皮生长因子受体 2（HER2）免疫组化（IHC）与 HER2 扩增和临床病理特征的相关性。
使用总共 71 例 OCCC 病例构建组织微阵列，用于 IHC（A0485 抗体和 4B5 抗体）和双色银原位杂交（DISH）。两位病理学家根据 2018 年美国临床肿瘤学会（ASCO）/美国病理学家协会（CAP）乳腺癌指南（乳腺癌指南）和 2016 年 ASCO/CAP 胃食管腺癌指南（胃指南）独立对 IHC 进行评分。A0485 和 4B5 之间的 IHC 一致性为 87.3-93.0%。3-16 例（4.2-22.5%）病例的 IHC 评分为 2+/3+，伴有频繁的基底外侧/侧膜弥漫性染色。4B5 抗体产生的 IHC 2+病例比 A0485 抗体少（n=2-6 与 n=5-12）。5 例（7.0%）病例通过 DISH 确定存在 HER2 扩增。具有乳头状为主生长模式的病例更有可能存在 HER2 扩增（P=0.0051）。在预测 DISH 结果方面，根据胃指南评分的 IHC 具有 100%/100%的灵敏度和 83.3-95.5%/98.2-100%的特异性，根据乳腺指南评分的 IHC 具有 60-80%/33.3-66.7%的灵敏度和 95.5-100%/100%的特异性（包括/不包括 IHC 2+病例）。1 例存在肿瘤内异质性，原发和转移肿瘤标本之间存在不一致的结果。
我们在 7%的 OCCC 病例中发现了 HER2 扩增，并且这种分子变化与乳头状为主的生长模式显著相关。在预测 HER2 扩增方面，4B5 IHC 与胃指南的组合提供了最佳的灵敏度，并且产生的可疑（IHC 2+）病例更少。鉴于肿瘤内异质性，建议在整个组织切片以及原发和转移肿瘤标本上评估 HER2 状态。
