Signal transduction pathway activity in adult-type granulosa cell tumor samples

Abstract

Objective: This study aims to evaluate signal transduction pathway (STP) activity in adult-type granulosa cell tumors (aGCT) in order to identify potential therapeutic targets. These results are compared with STP activity in healthy ovarian tissue and low and high grade serous ovarian carcinoma (LGSC and HGSC). Methods: STP activity was assessed by a RNA-based assay for the following oncogenic pathways: Hedhehog (HH), transforming growth factor beta (TGF-β), Notch, phosphoinositide 3-kinase (PI3K), mitogen-activated protein kinase (MAPK), androgen receptor (AR) and estrogen receptor (ER). Results: Samples of 31 aGCTs and a healthy granulosa cell were included and compared with 24 LGSC and 50 HGSC samples. In aGCT, significantly higher activity of the HH, Notch, PI3K and ER pathways was found, as compared to healthy granulosa cells. When compared with LGSC and HGSC, aGCT exhibited significantly higher PI3K pathway activity and lower HH, TGF-β, Notch, MAPK, AR, and ER pathway activity. Conclusions: Our results show high PI3K pathway activity in aGCT samples. Pathway activity contrasts with findings in both healthy granulosa cells and serous ovarian carcinoma. Therefore, the PI3K pathway may be a target for treatment, specifically for aGCT patients.