Ovarian carcinosarcoma is a distinct form of ovarian cancer with poorer survival compared to tubo-ovarian high-grade serous carcinoma

Abstract

Background Ovarian carcinosarcoma (OCS) is an uncommon, biphasic and highly aggressive ovarian cancer type, which has received relatively little research attention. Methods We curated the largest pathologically confirmed OCS cohort to date, performing detailed histopathological characterisation, analysis of features associated with survival and comparison against high-grade serous ovarian carcinoma (HGSOC). Results Eighty-two OCS patients were identified; overall survival was poor (median 12.7 months). In all, 79% demonstrated epithelial components of high-grade serous (HGS) type, while 21% were endometrioid. Heterologous elements were common (chondrosarcoma in 32%, rhabdomyosarcoma in 21%, liposarcoma in 2%); chondrosarcoma was more frequent in OCS with endometrioid carcinomatous components. Earlier stage, complete resection and platinum-containing adjuvant chemotherapy were associated with prolonged survival; however, risk of relapse and mortality was high across all patient groups. Histological subclassification did not identify subgroups with distinct survival. Compared to HGSOC, OCS patients were older (P < 0.0001), more likely to be FIGO stage I (P = 0.025), demonstrated lower chemotherapy response rate (P = 0.001) and had significantly poorer survival (P < 0.0001). Conclusion OCS represents a distinct, highly lethal form of ovarian cancer for which new treatment strategies are urgently needed. Histological subclassification does not identify patient subgroups with distinct survival. Aggressive adjuvant chemotherapy should be considered for all cases, including those with early-stage disease.

Cancer-associated fibroblasts are the main contributors to epithelial-to-mesenchymal signatures in the tumor microenvironment

“…Using a species-specific approach to parse mouse and human reads in a pan-cancer collection of gene expression data from xenograft samples, we demonstrated that, in the majority of tumor types, a greater proportion of transcripts from EMT-related genes originated from mouse stromal cells than from human tumor cells. In cancers known to have mesenchymal lineage components, such as ovarian carcinosarcomas 40 , expression of EMT-related genes did not originate predominantly from mouse stromal regions. Analysis of individual cell transcriptomes from tumor samples by scRNA-seq demonstrated that these EMT-related genes were highly expressed by CAFs.…”

Molecular characteristics and clinical behaviour of epithelial ovarian cancers

“…2B) [68,72]. Heterologous sarcomatous elements are present in around half of cases, most commonly chondrosarcoma (30% cases) or rhabdomyosarcoma (20% cases) [68,72]; it has been suggested that chondrosarcoma is more common in OCS with endometrioid type carcinomatous components (Fig. 2B) [68].…”

“…OCS is a rare diagnosis, accounting for <5% of cases, and represents the most aggressive form of OC (median survival approximately 13-24 months) [68,69]. Most are diagnosed at advanced stage (10-15% stage I, 10% stage II, 60-70% stage III, 10-20% stage IV), though recurrence and mortality risk is high across all stages [68,70,71]. Median age at OCS diagnosis is 66-70 years.…”

“…The epithelial component is typically of high grade serous type (80% cases), but is endometrioid in a significant proportion of cases (around 20%) (Fig. 2B) [68,72]. Heterologous sarcomatous elements are present in around half of cases, most commonly chondrosarcoma (30% cases) or rhabdomyosarcoma (20% cases) [68,72]; it has been suggested that chondrosarcoma is more common in OCS with endometrioid type carcinomatous components (Fig.…”

“…Heterologous sarcomatous elements are present in around half of cases, most commonly chondrosarcoma (30% cases) or rhabdomyosarcoma (20% cases) [68,72]; it has been suggested that chondrosarcoma is more common in OCS with endometrioid type carcinomatous components (Fig. 2B) [68]. IHC for cytokeratins and vimentin can be useful for confirming sarcomatous and carcinomatous populations, and markers used for other histotypes can be used to determine the epithelial component type (Table 1).…”