دورية أكاديمية
أعرض في EDS

Ovarian carcinosarcomas: p53 status defines two distinct patterns of oncogenesis and outcomes.

التفاصيل البيبلوغرافية
العنوان: Ovarian carcinosarcomas: p53 status defines two distinct patterns of oncogenesis and outcomes.
المؤلفون: Dhillon G; Department of Obstetrics & Gynaecology, University of British Columbia, Vancouver, BC, Canada., Llaurado-Fernandez M; Department of Obstetrics & Gynaecology, University of British Columbia, Vancouver, BC, Canada., Tessier-Cloutier B; Department of Pathology, Faculty of Medicine and Health Sciences, McGill University, Montreal, QC, Canada., Sy K; Department of Pathology, University of Toronto, Toronto, ON, Canada., Bassiouny D; Department of Pathology, Sunnybrook Health Science Centre, Toronto, ON, Canada., Han G; Department of Pathology and Laboratory Medicine, Surrey Memorial Hospital, Surrey, BC, Canada., Wong NKY; Department of Experimental Therapeutics, BC Cancer, Vancouver, BC, Canada., McRae K; Department of Obstetrics & Gynaecology, University of British Columbia, Vancouver, BC, Canada., Kinloch M; Department of Pathology and Laboratory Medicine, University of Saskatchewan, Saskatoon, SK, Canada., Pors J; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada., Hopkins L; Division of Gynaecologic Oncology, Saskatoon Cancer Centre, Saskatoon, SK, Canada., Covens A; Division of Gynaecologic Oncology, Sunnybrook Health Science Centre, University of Toronto, Toronto, ON, Canada., Köbel M; Department of Pathology and Laboratory Medicine, University of Calgary, Calgary, AB, Canada., Lee CH; Department of Pathology and Laboratory Medicine, University of University of Alberta, Edmonton, AB, Canada., Carey MS; Department of Obstetrics & Gynaecology, University of British Columbia, Vancouver, BC, Canada.; Department of Clinical Research, BC Cancer, Vancouver, BC, Canada.
المصدر: Frontiers in oncology [Front Oncol] 2024 Aug 16; Vol. 14, pp. 1408196. Date of Electronic Publication: 2024 Aug 16 (Print Publication: 2024).
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Frontiers Research Foundation] Country of Publication: Switzerland NLM ID: 101568867 Publication Model: eCollection Cited Medium: Print ISSN: 2234-943X (Print) Linking ISSN: 2234943X NLM ISO Abbreviation: Front Oncol Subsets: PubMed not MEDLINE
أسماء مطبوعة: Original Publication: [Lausanne : Frontiers Research Foundation]
مستخلص: Objectives: 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.
Study Methods: 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 p -value of less than 0.05 was considered statistically significant.
Results: 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; P < 0.01). Pathogenic BRCA1/2 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 BRCA1/2 wild-type HGSC-like OCS (33 patients) ( p = 0.022). Majority of patients (6/7) with BRCA1/2 -mutated OCS received poly (ADP-ribose) polymerase inhibitor as maintenance therapy in this cohort.
Conclusions: 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 BRCA1/2 testing on p53-mutated OCS.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2024 Dhillon, Llaurado-Fernandez, Tessier-Cloutier, Sy, Bassiouny, Han, Wong, McRae, Kinloch, Pors, Hopkins, Covens, Köbel, Lee and Carey.)
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فهرسة مساهمة: Keywords: BRCA; MMMT; PARPi; immunohistochemistry; ovarian cancer; ovarian carcinosarcoma; p53 IHC
تواريخ الأحداث: Date Created: 20240902 Latest Revision: 20240903
رمز التحديث: 20240903
مُعرف محوري في PubMed: PMC11361923
DOI: 10.3389/fonc.2024.1408196
PMID: 39220645
قاعدة البيانات: MEDLINE
الوصف
تدمد:2234-943X
DOI:10.3389/fonc.2024.1408196