Endocrine Abstracts

Background: In UK females, ovarian cancer (OC) is the 6th most common cancer and the most lethal gynaecological malignancy. Epithelial ovarian carcinoma (EOC) makes up 90% of OC. EOC is a heterogenous disease and is further categorised into subtypes. Mucinous Ovarian Carcinoma (MOC) is a rare EOC subtype, accounting for 3-5%. MOCs are often characterised as indolent, however, they are resistant to first-line platinum-based chemotherapies employed to treat EOC. Previous work from our laboratory suggests steroidal metabolism in MOC patients may be distinct from other EOC subtypes and healthy controls. Thus, understanding these pathways may lead to improved MOC diagnosis and treatment.

Methods: Expression of steroidogenesis enzymes and receptors in MOC cells were assessed by analysis of two publicly available datasets and validated through RT-qPCR. EOC cells androgen metabolism was investigated using liquid chromatography-tandem mass spectrometry. The effect of various steroids on MOC cell proliferation was determined through BrdU incorporation assays.

Results: SRD5A1/3 and HSD17B2/4 RNA expression is comparable between MOC and HGSOC. AKR1C3 is more highly expressed in MOC (2-10 TPM) compared to HGSOC (1-6 TPM). SRD5A2 was not expressed in MOC but was present at low levels in HGSOC (<1 TMP). The androgen receptor (AR) was lowly expressed, except in OVCAR3 (HGSOC, 3-4 TMP). RT-qPCR mimicked these findings; however, low levels of AR were expressed in all MOC lines, particularly in RMUG-S (>5 times AR expression of other MOC). Following testosterone treatment, synthesis of the less biologically active adione was >6 times higher in MOC than HGSOC despite comparable HSD17B2/4 expression. Seventy-two-hour androgen treatment resulted in up to a 50% reduction in RMUG-S proliferation; other MOC cell lines were not significantly affected.

Conclusion: Androgen metabolism is distinct between MOC and HGSOC. Furthermore, androgens may have an anti-proliferative effect on MOC, unlike in HGSOC.