Differential expression of nuclear retinoid receptors in normal and malignant prostates

Purpose: To determine(1) whether nuclear retinoic acid receptors (RARs) and retinoid X receptors (RXRs) are differentially expressed in normal and in cancerous human prostate tissues and (2) whether oral fenretinide therapy i mpacts the expression of these receptors in prostate cancer. Patients and Methods: In situ hybridization with antisense riboprobes was u sed to probe for RAR and RXR transcripts in prostate tissues in a two-phase d study: (1) expression of retinoid receptors in eight normal prostates was compared with their expression in 10 randomly picked radical prostatectomy specimens (group A); (2) expression of retinoid receptors was determined i n 22 radical prostatectomy specimens from participants in a clinical study (group B). Twelve patients received oral fenretinide 200 mg/d, and 10 recei ved placebo pills for 28 days before surgery. Results: RAR alpha, RAR gamma, RXR alpha, and RXR gamma mRNAs were detected in most normal and cancerous prostates. In group A, RAR beta mRNA was expr essed in only four of 10 malignant prostates but was present in seven of ei ght benign prostates (P = .05). RXR beta mRNA was expressed in four of eigh t benign prostates and in zero of 10 malignant prostates (P = .023). In gro up B prostates, RAR beta and RXR beta mRNAs were markedly reduced in all ca ncers and in the adjacent, nonmalignant tissue. There were no differences b etween receptor expression in the fenretinide-treated group and the placebo group. Conclusion: RAR beta and RXR beta mRNAs are selectively lost in both prosta te cancer and adjacent morphologically normal prostatic tissue, supporting the concept of a field of carcinogenesis. One month of oral fenretinide (20 0 mg/d) did not influence the expression of retinoid receptors in prostate cancer. (C) 2000 by American Society of Clinical Oncology.