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Decreased Expression of Retinoid Receptors in Melanoma: Entailment in Tumorigenesis and Prognosis

Authors' Affiliations: Departments of ¹ Head and Neck/Thoracic Medical Oncology and ² Pathology, and ³ Division of Quantitative Sciences, The University of Texas M. D. Anderson Cancer Center, Houston, Texas

Requests for reprints: Victor G. Prieto, Department of Pathology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030. Phone: 713-792-3187; Fax: 713-745-3740; E-mail: vprieto{at}mdanderson.org.

Purpose: Retinoids inhibit proliferation and induce differentiation in melanoma cells. Retinoic acid receptors (RAR) and retinoid X receptors (RXR) mediate the various modulatory effects of retinoids in cells. We have studied the in situ expression of each RAR and RXR protein (, ß, ) in a large series of melanocytic lesions and correlated the expression with clinicopathologic features and prognosis of the patients.

Experimental Design: Tissue microarray blocks of 226 melanocytic lesions were semiquantitatively evaluated by immunohistochemistry for the cytoplasmic and nuclear expression of RAR and RXR protein (, ß, ).

Results: A significant decrease of RARß protein (P < 0.0001), nuclear expression of RAR (P < 0.0001), and RXR (P < 0.0001) was found in primary and metastatic melanomas as compared with nevi. Loss of nuclear immunoreactivity for RAR (P = 0.048) and RXR (P = 0.001) was observed in the lesions showing vertical growth pattern. In addition, in patients with concomitant loss of cytoplasmic staining for RAR and RXR, the probability of overall survival (log-rank test, P = 0.002) and disease-specific survival (log-rank test, P = 0.014) was significantly lower.

Conclusions: Aberrant expression of retinoid receptors seems to be a frequent event in melanoma and suggests an impairment of the retinoid pathway in this cancer. Our data indicate the loss of retinoid receptor expression with melanoma progression and suggest a possible prognostic significance of the analysis of retinoid receptors in melanoma.