Dhillon Gurdial, Llaurado-Fernandez Marta, Tessier-Cloutier Basile, Sy Keiyan, Bassiouny Dina, Han Guangming, Wong Nelson K Y, McRae Kathryn, Kinloch Mary, Pors Jennifer, Hopkins Laura, Covens Allan, Köbel Martin, Lee Cheng-Han, Carey Mark S
Department of Obstetrics & Gynaecology, University of British Columbia, Vancouver, BC, Canada.
Department of Pathology, Faculty of Medicine and Health Sciences, McGill University, Montreal, QC, Canada.
Front Oncol. 2024 Aug 16;14:1408196. doi: 10.3389/fonc.2024.1408196. eCollection 2024.
Ovarian carcinosarcoma (OCS) is a rare and lethal type of ovarian cancer. Despite its incredibly poor prognosis, it has received little research attention. In this study, we aim to evaluate the molecular features of OCS and elucidate their clinical significance.
We examined 30 OCS by immunohistochemistry (IHC) and targeted panel sequencing collected from a single institution (2003-2013) as the initial molecularly characterized cohort (Cohort A). From November 2016 to April 2023, we collected an additional 67 OCS cases from three institutions across British Columbia and Alberta as the contemporary cohort (Cohort B) for clinical correlation. The Kaplan-Meier method was used to estimate overall and progression-free survival, and differences in survival rates were compared using the log-rank test. All tests were two-sided. A -value of less than 0.05 was considered statistically significant.
The majority of OCS (82%) in the initial Cohort A were p53-mutated, and the carcinomatous component displayed the histological and molecular features of a high-grade tubo-ovarian serous carcinoma (HGSC-like). In a minority of OCS, the epithelial components were characteristics of endometrioid or clear cell carcinomas, and IHC staining was wild type for p53. In the contemporary Cohort B, we observed the same histological findings related to the p53 IHC staining pattern. The median overall survival of the p53-mutated HGSC-like OCS (47 patients) was significantly higher (43.5 months) compared with that of the p53 wild-type OCS (10 patients, 8.8 months; < 0.01). Pathogenic germline/somatic mutations were observed in 7 patients (17.5%) of HGSC-like OCS, and all these patients were alive at 3 years from diagnosis compared to a 51% 3-year survival among the patients with wild-type HGSC-like OCS (33 patients) ( = 0.022). Majority of patients (6/7) with -mutated OCS received poly (ADP-ribose) polymerase inhibitor as maintenance therapy in this cohort.
Most OCSs have a morphologic and molecular profile resembling HGSC; however, some OCSs display a molecular profile that suggests origin through non-serous oncogenic pathways. This molecular distinction has both prognostic and treatment (predictive) implications. These findings underscore the importance of routine p53 IHC testing on all OCS and testing on p53-mutated OCS.
卵巢癌肉瘤（OCS）是一种罕见且致命的卵巢癌类型。尽管其预后极差，但受到的研究关注较少。在本研究中，我们旨在评估OCS的分子特征并阐明其临床意义。
我们通过免疫组织化学（IHC）和靶向基因panel测序检查了从单个机构收集的30例OCS（2003 - 2013年），作为初始分子特征队列（队列A）。从2016年11月到2023年4月，我们从不列颠哥伦比亚省和艾伯塔省的三个机构收集了另外67例OCS病例，作为当代队列（队列B）用于临床相关性分析。采用Kaplan - Meier方法估计总生存期和无进展生存期，并使用对数秩检验比较生存率差异。所有检验均为双侧检验。P值小于0.05被认为具有统计学意义。
初始队列A中的大多数OCS（82%）存在p53突变，癌性成分表现出高级别输卵管卵巢浆液性癌（HGSC样）的组织学和分子特征。在少数OCS中，上皮成分具有子宫内膜样或透明细胞癌的特征，且p53的IHC染色为野生型。在当代队列B中，我们观察到与p53 IHC染色模式相关的相同组织学发现。p53突变的HGSC样OCS（47例患者）的中位总生存期（43.5个月）显著高于p53野生型OCS（10例患者，8.8个月；P < 0.01）。在HGSC样OCS的7例患者（17.5%）中观察到致病性种系/体细胞突变，与p53野生型HGSC样OCS（33例患者）中51%的3年生存率相比，所有这些患者在诊断后3年仍存活（P = 0.022）。在该队列中，大多数（6/7）p53突变的OCS患者接受了聚（ADP - 核糖）聚合酶抑制剂作为维持治疗。
大多数OCS具有类似于HGSC的形态学和分子特征；然而，一些OCS表现出提示通过非浆液性致癌途径起源的分子特征。这种分子差异具有预后和治疗（预测）意义。这些发现强调了对所有OCS进行常规p53 IHC检测以及对p53突变的OCS进行基因检测的重要性。
