Mutational and Immunophenotypic Profiling of a Series of 8 Tubo-ovarian Carcinosarcomas Revealed a Monoclonal Origin of the Disease

Abstract

Carcinosarcomas are rare, highly aggressive neoplasms composed of a combination of carcinomatous and sarcomatous elements. These tumors represent a paradigmatic field for the study of intratumor heterogeneity. A series of 8 tubo-ovarian carcinosarcomas was characterized for the following: (i) immunohistochemical expression of MNF116, epithelial membrane antigen, vimentin, S100, chromogranin, synaptophysin, desmin, myogenin (MYF4), and p53; (ii) mutational profiling of KRAS, BRAF, PIK3CA, NRAS, TP53, and DICER1 genes. Heterologous differentiation was present in 6 of 8 tumors. Cytokeratin MNF116 and epithelial membrane antigen were positive in all the carcinomatous components and in 87.5% and 50.0% of the sarcomatous components, respectively. The sarcomatous components showed positive staining for vimentin in all cases. Two cases demonstrated positivity for neuroendocrine markers in their carcinomatous components. All rhabdomyosarcomas were positive for desmin and MYF-4. Chondrosarcomas were positive for S100. All but one tumor showed similar p53 immunoreactivity in both the carcinomatous and sarcomatous components, and one case showed cytoplasmic p53 expression. Three of 8 cases (37.5%) showed TP53 mutations, and, in 2 cases, the TP53 mutation was shared by both epithelial and mesenchymal components. DICER1 mutation was found in all components of one case. Mutations in KRAS, NRAS, BRAF, and PIK3CA genes were not found in the study cohort. Our results highlight the heterogeneity of ovarian carcinosarcomas at the phenotypic level. A common mutational signature was observed in both components in 3 of 4 informative tumors. More studies are required to dissect different levels of ovarian carcinosarcomas’ heterogeneity in order to define the best therapeutic approaches to these aggressive neoplasms.

Management of a rare ovarian carcinosarcoma: A case report and literature review

“…The present study indicated that the serous carcinoma component was positive for CK and P53, squamous cell carcinoma was positive for P40, chondrosarcoma was positive for S100 and rhabdomyosarcoma was positive for MyoD1. The findings of the present study were similar to those of previous studies ( 3 , 10 , 11 ). In a study of 8 cases with OCS ( 3 ), the carcinomatous components exhibited positive staining for epithelial markers, including cytokeratin MNF116.…”

“…The findings of the present study were similar to those of previous studies ( 3 , 10 , 11 ). In a study of 8 cases with OCS ( 3 ), the carcinomatous components exhibited positive staining for epithelial markers, including cytokeratin MNF116. All sarcomatous components had positive staining for vimentin and all rhabdomyosarcomas were positive for myogenic markers, including MYF4.…”

“…All chondrosarcomas were positive for S100. All tumors displayed were positive for p53( 3 ). Pankaj et al ( 10 ) indicated that CK and vimentin were positive, indicating the likely presence of carcinosarcoma and epithelioid sarcoma.…”

“…According to the sarcoma components, it may be classified as homologous (the sarcoma component was derived from the stromal component of the primary tumor site, e.g., endometrial stromal sarcoma) or heterologous (the sarcoma component was not derived from the interstitial component of the primary tumor site, such as rhabdomyosarcoma component, osteosarcoma component) ( 2 ). Immunohistochemical (IHC) analysis of markers including cytokeratin (CK), cytokeratin pan monoclonal antibody (MNF116), epithelial membrane antigen, vimentin, S100, chromogranin, synaptophysin, desmin, myogenin (MYF4) and p53 were used to suggest the presence of the heterologous component ( 3 ). The current treatment methods mainly include ovarian tumor cytoreduction surgery, followed by platinum-based chemotherapy.…”

Three-Dimensional Modelling of Ovarian Cancer: From Cell Lines to Organoids for Discovery and Personalized Medicine

“…Almost all HGSOC have a somatic TP53 mutation and p53 immunohistochemistry is a surrogate marker for TP53 mutation in these tumors ( Bell, 2011 ; Cole et al, 2016 ; Köbel and Kang, 2021 ). TP53 mutations are also observed in MOC ( Köbel and Kang, 2021 ), ovarian carcinosarcomas ( Trento et al, 2020 ) and less frequently in OCCC ( Parra-Herran et al, 2019 ). BRCA1 and BRCA2 mutations occur in HGSOC, including in the germline of affected patients ( Alsop et al, 2012 ), and rarely in patients with OCCC ( De Pauw et al, 2021 ).…”