Clear cell carcinoma of the ovary : epidemiology and biomarker HNF-1beta

Abstract

Ovarian clear cell carcinoma (OCCC) is an epithelial ovarian cancer (EOC) often associated with endometriosis, chemoresistance and poor prognosis. This study aims at evaluating epidemiological trend OCCC in Hong Kong, investigating biological roles of Hepatocyte nuclear factor-1β (HNF-1β) in OCCC cells and exploring for possible crosstalk between iASPP and HNF-1β.

Study of archived hospital pathology reports showed that OCCC accounted for 22.4% of all EOC, concurring with epidemiological findings suggesting relative susceptibility of Asians to this ovarian cancer subtype. An increasing trend in the incidences of OCCC, EOC and endometriosis was also found.

HNF-1β is overexpressed in nearly all OCCC and can be used as a histotype-specific biomarker assisting histopathological diagnosis of OCCC. Functional studies of HNF-1β performed via transient knockdown of HNF-1β in OVMANA cells shed light on the potential roles of HNF-1β in cell survival, oxidative stress regulation, glycolysis and cell mobility. HNF-1β knockdown in OCCC cells was noted to induce apoptosis in a likely caspase independent manner. Glycolysis was also promoted by HNF-1β overexpression which may also regulate reactive oxygen species (ROS) levels to prevent oxidative damages on OCCC cells. iASPP, a proto-oncogene known to prevent apoptosis in a p53-dependent manner, was found to be positively affected by HNF-1β expression though the exact mechanisms are yet to be elucidated.

In summary, HNF-1β contributes to essential cellular functions in OCCC, and a thorough understanding of its function may provide insight to novel treatment strategies for this enigmatic tumor whose incidence is on the rising trend in Hong Kong.