INVESTIGATIVE UROLOGY

Immunohistochemical localization of the retinoic acid receptors in human prostate
Richter F, Joyce A, Fromowitz F, Wang S, Watson J, Watson R, Irwin Jr RJ, Huang HFS
From the Department of Surgery, Division of Urology and Laboratory of Medicine and Pathology, UMDNJ, New Jersey Medical School, Newark, New Jersey, and VA Medical Center, East Orange, New Jersey
J Androl. 2002; 23:830-8

• Retinoic acid receptors (RARs) are nuclear transcription factors that mediate the effects of retinoids. Aberrant expression and regulation of RARs have been linked to various malignancies, including steroid-related breast and cervical cancers. Our previous results also suggest that prostate cancer is associated with altered RAR signaling. To understand the relationship between RAR signaling and prostate cancer, the current study examined the cellular distribution of RAR-a, -b, and -g in human prostate tissues exhibiting different pathologic conditions. In histologically normal epithelium, both RAR-a and -g were present throughout the epithelium with minimal nuclear accumulation. RAR-b was present only in basal epithelial nuclei. On the contrary, RAR-a was significantly increased in the nuclei of luminal epithelial cells, and both RAR-b and -g were increased in basal and luminal epithelial nuclei in glands exhibiting benign prostatic hyperplasia (BPH). RAR-a as also increased in luminal epithelial nuclei in glands exhibiting prostatic intra-epithelial neoplasia (PIN). In these glands, RAR-b was persisting in basal epithelial nuclei that were also RAR-g positive. In low- and intermediate-grade cancerous glands, RAR-a was also significantly increased in luminal epithelial nuclei, and a strong RAR-g signal was seen in some cells. RAR-b was absent in these glands. Both RAR-a and -g were also increased in high-grade cancer cells. In conclusion, current results demonstrated changes in cellular distribution of RAR-a and -g in human prostate tissues exhibiting different pathologies. These results suggest links between altered RAR signaling and deregulated cell growth and/or tumorigenic transformation of prostate epithelial cells.
  
  
• Editorial Comment
  The authors examined the cellular distribution of retinoic acid receptors (RAR) RAR-a, -b, and -g in normal (patients submitted to cystoprostatectomy for bladder carcinoma) and pathologic (adenocarcinoma, prostatic intraepithelial neoplasia, and benign prostatic hyperplasia) human prostate tissues, with the purpose of comprehending the role of RAR signaling in human prostate cancer biology. The results of the analysis performed demonstrated differences in the cellular distribution of these receptors in prostatic tissue exhibiting different pathophysiology. The findings emphasize the importance of RAR signaling in prostate cell biology, and perhaps in the genesis and progression of prostate cancer. Also, the distinct distribution pattern of these receptors under different pathologic conditions may qualify them as adjuvant markers for specific disease states.

Dr. Francisco J.B. Sampaio
Chairman, Urogenital Research Unit
State University of Rio de Janeiro
Rio de Janeiro, Brazil