Molecular profiling and molecular classification of endometrioid ovarian carcinomas

Objective. Endometrioid ovarian carcinomas (EOCs) comprise 5-10% of all ovarian cancers and commonly cooccur with synchronous endometrioid endometrial cancer (EEC). We sought to examine the molecular characteristics of pure EOC5 in patients without concomitant EEC. Methods. EOCs and matched normal samples were subjected to massively parallel sequencing targeting 341-468 cancer-related genes (n = 8) or whole-genome sequencing (n = 28). Mutational frequencies of EOCs were compared to those of high-grade serous ovarian cancers (HGSOCs; n = 224) and EECs (n = 186) from The Cancer Genome Atlas, and synchronous EOCs (n = 23). Results. EOC5 were heterogeneous, frequently harboring KRAS, PIK3CA, PTEN, CTNNB1, ARID1A and TP53 mutations. EOC5 were distinct from HGSOCs at the mutational level, less frequently harboring TP53 but more frequently displaying KRAS, PIK3CA, PIK3R1, PTEN and CTNNB1 mutations. Compared to synchronous EOCs and pure EECs, pure EOC5 less frequently harbored PTEN, PIK3R1 and ARIDIA mutations. Akin to EECs, EOCs could be stratified into the four molecular subtypes: 3% POLE (ultramutated), 19% MSI (hypermutated), 17% copynumber high (serous-like) and 61% copy-number low (endometrioid). In addition to microsatellite instability, a subset of EOCs harbored potentially targetable mutations, including AKTI and ERBB2 hotspot mutations. EOCs of MSI (hypermutated) subtype uniformly displayed a good outcome. Conclusions. EOCs are heterogeneous at the genomic level and harbor targetable genetic alterations. Despite the similarities in the repertoire of somatic mutations between pure EOCs, synchronous EOCs and EECs, the frequencies of mutations affecting known driver genes differ. Further studies are required to define the impact of the molecular subtypes on the outcome and treatment of EOC patients. (C) 2019 Elsevier Inc. All rights reserved.