Expression of nuclear hormone receptors in ovarian cancer

Introduction: Advanced ovarian cancer (OC) has an unfavourable prognosis and limited response to systemic therapeutic agents. Previous work observed an overexpression of LH- and FSH-receptors with high prognostic significance. In the current analysis, we focus on members of the nuclear superfamily (TR (thyroid receptor) α and β, VDR, RXR, PPARγ) to evaluate their expression on tumor tissue and correlate it with immunohistochemical findings and prognosis.

Methods: Tissue samples were taken intraoperatively from ovarian cancer patients (n = 154) and immunhistochemical stainings (ABC method) were performed. SPSS was used for statistical analyses.

Results: All investigated receptors were expressed reciprocally in the nucleus and the cytoplasmatic compartment. Regarding histological subtype, TRβ was only expressed in clear cell carcinomas (IRS 2.08, p < 0.001), predominantly in the cytoplasmatic compartment (in 75% of all samples). In serous carcinomas, there was a shift of TRα2 expression from intra-nuclear expression in low grade tumors to cytoplasmatic expression in high grade. The cytoplasmatic expression was significantly correlated with shorter overall survival (OR 5.38, p < 0.001, IRS< 4 (p = 0.01)). Higher mortality rate was observed for patients with cytoplasmatic expression of VDR (OR 4.09, p = 0.05) and TRβ (OR 2.66, p = 0.03). No significant correlations were found for RXR, PPARγ and TRα1.

Discussion: Intra-nuclear TRα2 expression in serous carcinoma was correlated with longer survival whereas the cytoplasmatic expression of TRα2, TRβ and VDR increased the mortality risk. Apparently, there is a receptor shift from intra-nuclear expression in low grade OC tumors to cytoplasmatic expression in more aggressive disease. This shift might be triggered by Inflammation.