Retinoid receptors in ovarian cancer:: expression and prognosis

Background: Ovarian cancer is frequently lethal despite aggressive multimodal therapy, and new therapies are therefore needed. Retinoids are potential candidate drugs: they prevent the development of ovarian carcinoma and enhance the efficacy of cytotoxic drugs in ovarian cancer cells. At present, little is known about the retinoid receptor expression in ovarian cancer. Patients and methods: The retinoid receptors comprise two classes, retinoic acid receptors (RARs) and retinoid X receptors (RXRs), each with three subclasses, alpha, beta and gamma. We investigated the expression of the subtypes RAR alpha, RAR gamma, RXR alpha and RXR beta by immunohistochemistry in ovarian cancers of 80 patients, and assessed their prognostic significance. In addition, we quantified the expression of retinoid receptor mRNA using real-time PCR and correlated the results with clinical characteristics. Results: RAR alpha and RXR beta were highly expressed in a majority of ovarian cancers, particularly in advanced stages. High expression of RAR alpha was an independent negative prognostic factor of survival in addition to FIGO stage, age and p53 accumulation. The mRNA expression of retinoid receptors did not correlate with clinical properties of the tumors. Conclusions: Retinoic acid receptors are frequently and strongly expressed in epithelial ovarian cancer and may be indicators of an adverse prognosis. This study provides the molecular basis for the therapeutic use of retinoids in ovarian cancer.