Disease site matters: Ovarian carcinosarcoma has far more genomic similarity to high-grade serous ovarian carcinoma than to uterine carcinosarcoma

Abstract

<h3>Objectives:</h3> To determine if the genomic behavior of ovarian carcinosarcoma (OCS), based on mutations identified in next-generation sequencing (NGS) tumor profiling, is more similar to its histologic counterpart, uterine carcinosarcoma (UCS) or high-grade serous ovarian carcinoma (HGSOC). <h3>Methods:</h3> Preliminary data was collected from AACR's Project GENIE v8.0, a collection of multi-institutional Next Genome Sequencing (NGS) genomic profiling data, via cBioPortal (http://genie.cbioportal.org). Ovarian Carcinosarcoma (OCS), High Grade Serous Ovarian Cancer (HGSOC) and Uterine Carcinosarcoma (UCS) were selected and analyzed for mutation frequencies. The initial analysis determined which genes had a difference in mutation frequency between the HGSOC and UCS groups using a Fisher's Exact Test. We then selected the genes with p-value less than 0.0005 to create a signature to distinguish between HGSOC and UCS. This gene signature was then used to determine whether each OCS sample was more genetically similar to HGSOC or UCS. <h3>Results:</h3> In the analysis, there were 454 patients with HGSOC, 40 patients with OCS, and 72 patients with UCS. Five genes (FBXW7, KRAS, PIK3CA, PIK3R1, and PTEN) were the only genes idenitifed that predicted the difference between HGSOC and UCS with a p-value <0.0005. Mutational frequencies for the 5 predictive genes in UCS vs HGSOC vs OCS were: FBXW7 (19% vs 2% vs 3%), KRAS (17% vs 2% vs 8%), PIK3CA (32% vs 4% vs 5%), PIK3R1 (19% vs 1% vs 0%), and PTEN (17% vs 3% vs 5%). A specimen containing 1 or more of the 5 predictive gene mutations had a sensitivity of 65% and specificity of 90% for predicting UCS vs HGSOC (Table 1). Amongst the 40 OCS samples, 4 (10%) behaved like UCS, while 36 (90%) behaved like HGSOC according to this signature. <h3>Conclusions:</h3> OCS appears to be more similar genomically to HGSOC than UCS. These findings support current NCCN guidelines that recommend adjuvant treatment of OCS follow the same paradigm as HGSOC. Furthermore, these findings add to the growing consensus that patients with OCS should be considered for inclusion in clinical trials for epithelial ovarian cancer.