AUTHOR=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. 

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

JOURNAL=Frontiers in Oncology

VOLUME=Volume 14 - 2024

YEAR=2024

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2024.1408196

DOI=10.3389/fonc.2024.1408196

ISSN=2234-943X

ABSTRACT=Objective(s): 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. Majority of patients (6/7) with BRCA1/2 mutated OCS received PARPi
as maintenance therapy in this cohort. 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 tuboovarian serous carcinoma (HGSC-like). In a minority of OCS, the epithelial components were 
characteristic 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 to the p53 wild-type OCS (10 patients, 8.8 
months; P <.01). Pathogenic BRCA1/2 germline/somatic mutations were observed in 10 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 = .022). 
Conclusion: Most OCS have a morphologic and molecular profile resembling HGSC; however, 
some OCS 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.