Abstract
Recurrent NCOA1/2/3 gene fusions emerged in uterine tumor resembling ovarian sex cord tumor (UTROSCT). More cases are required to consolidate these molecular alterations. In this study, the clinicopathological features and immunostaining profiles were reviewed in 18 UTROSCT. Fluorescence in situ hybridization for dual color break-apart probes of NCOA1, NCOA2, NCOA3, BCOR, YWHAE, PHF1 and JAZF1 were performed on 16 tumors. Eight cases were subjected to targeted next-generation sequencing to detect genomic alterations. We found that the tumors predominantly showed various sex-cord patterns without a recognizable endometrial stromal component. They exhibited a diverse immunohistochemical profile, frequently co-expressing sex cord (calretinin, inhibin, WT1, SF-1, and FOXL2), smooth muscle (SMA, desmin and caldesmon), epithelial (CK) and other markers (CD10 and IFITM1). Fourteen of 16 tumors (87.5%) showed NCOA1-3 gene rearranges, but none had BCOR, YWHAE, PHF1 and JAZF1 fusions. Five tumors contained 6 non-recurrent pathogenic (likely) mutations and one had gains in c-MYC. Our study supports frequent NCOA1-3 rearrangements in UTROSCT. Rare, non-recurrent mutations suggest that these gene rearrangements be potential drivers in tumorigenesis. Detection of gene rearrangements can contribute to the correct interpretation of UTROSCT. However, large comparative studies with molecular tests are required to confirm these findings.