Decreased expression of retinoid receptors in melanoma: entailment in tumorigenesis and prognosis

Clin Cancer Res. 2007 Aug 15;13(16):4817-24. doi: 10.1158/1078-0432.CCR-06-3026.


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 (alpha, beta, gamma) 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 (alpha, beta, gamma).

Results: A significant decrease of RARbeta protein (P < 0.0001), nuclear expression of RARgamma (P < 0.0001), and RXRalpha (P < 0.0001) was found in primary and metastatic melanomas as compared with nevi. Loss of nuclear immunoreactivity for RARgamma (P = 0.048) and RXRalpha (P = 0.001) was observed in the lesions showing vertical growth pattern. In addition, in patients with concomitant loss of cytoplasmic staining for RARalpha and RXRalpha, 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Disease Progression
  • Humans
  • Melanoma / chemistry
  • Melanoma / mortality
  • Melanoma / pathology*
  • Melanoma / secondary
  • Nevus / pathology
  • Prognosis
  • Proportional Hazards Models
  • Receptors, Retinoic Acid / analysis*
  • Retinoid X Receptor alpha / analysis*
  • Tissue Array Analysis


  • Receptors, Retinoic Acid
  • Retinoid X Receptor alpha