Cellular Distribution of Retinoic Acid Receptor–α in Benign Hyperplastic and Malignant Human Prostates: Comparison with Androgen, Estrogen and Progesterone Receptor Status

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Abstract
Retinoids are unique modulators of gene activity, cell growth and differentiation by binding to a series of nuclear receptors, i.e. all-trans-retinoic acid receptors (RAR) or 9-cis-retinoid receptors (RXR). In this study, the expression of RARalpha was immunohistochemically evaluated in benign, hyperplastic and malignant prostatic tissue and correlated with sex steroid receptor status. Twenty-four cases of BPH and 139 cases of primary prostatic carcinoma were evaluated for RARalpha expression in correlation with androgen (AR), estrogen (ER) and progesterone (PGR) receptor staining, as well as with tumor grade. RARalpha was detected in the nuclei of epithelial cells in both BPH and prostate carcinoma cases. A modest inverse relationship with grade was present, especially for grade I and grade II tumors. AR staining was intense and a strong inverse relationship with grade was revealed. Although ER and PGR showed nuclear staining in prostatic epithelium, the overall expression for these receptors was low. When RARalpha content was compared to the nuclear AR expression, at least two-fold higher RARalpha levels were observed in AR+ grade II and grade III tumors. RARalpha expression can be immunohistochemically evaluated in formalin-fixed paraffin-embedded prostatic tissue. RARalpha expression is significantly elevated in AR+ moderately and poorly differentiated prostate carcinomas. Immunohistochemical determination of RARalpha content may be useful in defining the patient subsets in which retinoid-based treatment may be of clinical value.

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