Clinicopathologic and Molecular Features of Tubo-Ovarian Carcinosarcomas With an Emphasis on p53 Wild-Type, KRAS-Mutated Tumors.

Tubo-ovarian carcinosarcomas (OCS) are uncommon, aggressive tumors. Recent literature in uterine carcinosarcomas has shown prognostic differences by the molecular classification established by The Cancer Genome Atlas. Our aim was to delineate the molecular subtypes within OCS and associated clinicopathologic, immunohistochemical, and additional molecular features. A total of 57 OCS were identified at our institution. The overall median follow-up period was 32.3 months, and 5-year survival rates were 71% (stage I/II), 42% (stage III), and 17% (stage IV). Fifty-one (89%) tumors were of the p53-abnormal molecular subtype. Five (9%) tumors were of no specific molecular subtype, and all 5 of these tumors harbored canonical mutations in KRAS (codon 12). We also identified the first reported primary POLE-mutated OCS in a patient with Lynch syndrome; this case was assigned as of a double-classifier POLE-mutated/mismatch repair-deficient molecular subtype. No tumors were of the single-classifier mismatch repair-deficient or POLE-mutated molecular subtype. Compared with the p53-abnormal tumors, KRAS-mutated tumors occurred in younger women at lower stages, but did recur in 2 out of 5 (40%) patients. They always showed endometrioid rather than high-grade serous morphology and were usually ER, PR, and WT1 negative. Three KRAS-mutated tumors also had at least focal mesonephric-like histology. Although rare, p53 wild-type tumors represent a small subset of OCS that show distinct clinical and histologic features and are largely driven by KRAS mutations.