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Annals of Oncology Advance Access published online on July 12, 2005
Annals of Oncology, doi:10.1093/annonc/mdi265
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© 2005 European Society for Medical Oncology
Received March 21, 2005
Revised April 13, 2005
Accepted April 14, 2005

Original article

Retinoid receptors in ovarian cancer: expression and prognosis

P. C. Kaiser 1, M. Körner 2, A. Kappeler 2, and S. Aebi 3*

1 University Hospital Berne, Department of Medical Oncology, Bern, Switzerland University of Bern, Department of Clinical Research, Bern, Switzerland
2 University of Bern, Institute of Pathology, Bern, Switzerland
3 University Hospital Berne, Department of Medical Oncology, Bern, Switzerland University of Bern, Department of Clinical Research, Bern, Switzerland

* To whom correspondence should be addressed.
S. Aebi, E-mail: stefan.aebi{at}insel.ch


  Abstract

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.

Keywords: nuclear receptors; ovarian neoplasms; prognostic factors; retinoic acid receptors.
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