Uterine lavage identifies cancer mutations and increased TP53 somatic mutation burden in individuals with ovarian cancer.

Current screening methods for ovarian cancer (OC) have failed to demonstrate a significant reduction in mortality. Uterine lavage combined with TP53 ultra-deep sequencing for the detection of disseminated OC cells has emerged as a promising tool, but this approach has not been tested for early-stage disease or non-serous histologies. In addition, lavages carry multiple background mutations, the significance of which is poorly understood. Uterine lavage was collected preoperatively in 34 patients undergoing surgery for suspected ovarian malignancy including 14 patients with benign disease and 20 patients with OC (6 non-serous and 14 high grade serous-like (serous)). Ultra-deep duplex sequencing (~3000x) with a panel of common OC genes identified the tumor mutation in 33% of non-serous (all early stage) and in 79% of serous cancers (including four early stage). In addition, all lavages carried multiple somatic mutations (average of 25 mutations per lavage), more than half of which corresponded to common cancer driver mutations. Driver mutations in KRAS, PIK3CA, PTEN, PPP2R1A and ARID1A presented as larger clones than non-driver mutations and with similar frequency in lavages from patients with and without OC, indicating prevalent somatic evolution in all patients. Driver TP53 mutations, however, presented as significantly larger clones and with higher frequency in lavages from individuals with OC, suggesting that TP53-specific clonal expansions are linked to ovarian cancer development. Our results demonstrate that lavages capture cancer cells, even from early-stage cancers, as well as other clonal expansions and support further exploration of TP53 mutation burden as a potential OC risk factor.

Epithelioid angiosarcoma arising in a uterine leiomyoma with associated elevated CA-125: A case report.

We describe the case of a 67 year old female with longstanding uterine leiomyomas who presented with fatigue, weight loss, elevated CA-125 and an enlarging mass arising from the posterior uterine fundus. Histologic sections of the mass contained a leiomyoma with interspersed foci of malignant epithelioid cells forming anastomosing vascular channels. The neoplastic cells were diffusely positive for CD31 and FLI1, supporting the morphologic impression of epithelioid angiosarcoma. Few cases of epithelioid angiosarcoma arising within a leiomyoma have been described. In this report we discuss this association and describe its relation with elevated CA-125.