Int J Gynecol Pathol. 2024 May 1;43(3):275-283. doi: 10.1097/PGP.0000000000000972. Epub 2024 Mar 4.
Mucinous ovarian carcinoma is an uncommon malignancy characterized by resistance to chemotherapy and poor survival in the metastatic setting. HER2 amplification is a frequent late event in carcinogenesis, yet the incidence of HER2-low in mucinous ovarian carcinoma is unknown. Further, the optimal method for determining overexpression in these tumors is not established. We sought to assess the ASCO/CAP and ToGA trial scoring methods for HER2 IHC with correlation to FISH, p53, and mismatch repair protein status and to determine the incidence of HER2-low in mucinous ovarian carcinoma. A total of 29 tumors from 23 patients were included. Immunohistochemistry for HER2, p53, MLH1, PMS2, MSH2, and MSH6 was performed. Scoring was performed according to the ASCO/CAP and ToGA trial criteria. HER2 FISH was performed and scored according to the ASCO/CAP criteria. The proportion of HER2-low, defined as 1+ or 2+ staining with negative FISH, was determined. Using ASCO/CAP, 26% demonstrated 3+ while 35% demonstrated 2+ staining. Using ToGA, 30% demonstrated 3+ while 57% demonstrated 2+ staining. By FISH, 26% were positive for HER2 amplification. Both systems captured all FISH-positive cases; the use of ASCO/CAP resulted in fewer equivocal and false-positive cases. Among HER2-negative cases, 88% were HER2-low. Aberrant p53 expression was detected in 55% of cases; mismatch repair deficiency was not identified in any cases. ASCO/CAP guidelines are accurate and resource-effective in determining HER2 overexpression in mucinous ovarian carcinoma. HER2-low is common in these tumors; further studies to determine the role of HER2-targeted therapy including antibody-drug conjugates are indicated.
黏液性卵巢癌是一种罕见的恶性肿瘤，其特点是对化疗具有耐药性，且在转移性疾病中生存情况较差。HER2 扩增是致癌作用中的一个常见晚期事件，然而，黏液性卵巢癌中 HER2 低表达的发生率尚不清楚。此外，这些肿瘤中确定过表达的最佳方法尚未建立。我们旨在评估 ASCO/CAP 和 ToGA 试验 HER2 IHC 的评分方法，并与 FISH、p53 和错配修复蛋白状态相关联，以确定黏液性卵巢癌中 HER2 低表达的发生率。共纳入 23 名患者的 29 例肿瘤。进行了 HER2、p53、MLH1、PMS2、MSH2 和 MSH6 的免疫组化检测。根据 ASCO/CAP 和 ToGA 试验标准进行评分。进行了 HER2 FISH 检测，并根据 ASCO/CAP 标准进行评分。确定了 HER2 低表达的比例，定义为 FISH 阴性的 1+或 2+染色。根据 ASCO/CAP，26%表现为 3+，35%表现为 2+染色。根据 ToGA，30%表现为 3+，57%表现为 2+染色。通过 FISH，26%的病例 HER2 扩增呈阳性。两种系统均捕获了所有 FISH 阳性病例；使用 ASCO/CAP 导致更少的不确定和假阳性病例。在 HER2 阴性病例中，88%为 HER2 低表达。在 55%的病例中检测到异常的 p53 表达；任何病例均未发现错配修复缺陷。ASCO/CAP 指南在确定黏液性卵巢癌中的 HER2 过表达方面是准确且资源有效的。这些肿瘤中 HER2 低表达很常见；需要进一步研究以确定包括抗体药物偶联物在内的 HER2 靶向治疗的作用。
