Cellular distribution of retinoic acid receptor-alpha in benign hyperplastic and malignant human prostates: Comparison with androgen, estrogen and progesterone receptor status

Objectives: 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 8-cis-retinoid receptors (RXR). In this study, the expression of RAR alpha was immunohistochemically evaluated in benign, hyperplastic and malignant prostatic tissue and correlated with sex steroid receptor status. Methods: Twenty-four cases of BPH and 139 cases of primary prostatic carcinoma were evaluated for RAR alpha expression in correlation with androgen (AR), estrogen (ER) and progesterone (PGR) receptor staining, as well as with tumor grade. Results: RAR alpha 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 RAR alpha content was compared to the nuclear AR expression, at least two-fold higher RAR alpha levels were observed in AR+ grade II and grade III tumors. Conclusions: RAR alpha expression can be immunohistochemically evaluated in formalin-fixed paraffin-embedded prostatic tissue. RAR alpha expression is significantly elevated in AR+ moderately and poorly differentiated prostate carcinomas. Immunohistochemical determination of RAR alpha content may be useful in defining the patient subsets in which retinoid-based treatment may be of clinical value. Copyright (C) 2000 S. Karger AG, Basel.