INVESTIGATIVE UROLOGY

Does benign prostatic hyperplasia originate from the peripheral zone of the prostate? A preliminary study
Tang J, Yang JC, Zhang Y, Liu X, Zhang L, Wang Z, Li J, Luo Y, Xu J, Shi H
Department of Ultrasound, Chinese People’s Liberation Army General Hospital, Beijing, PR China
BJU Int. 2007; 100: 1091-6

• Objective: To compare the histological characteristics, cell proliferation, apoptosis and biological features in benign prostatic hyperplasia (BPH) in the peripheral (PZ) and transition zone (TZ) of the prostate.
• Patients and Methods: Tissue from BPH in TZ and PZ was obtained from 68 patients undergoing transrectal ultrasonography-guided biopsy and used for both morphometric analysis and immunohistochemical studies. The epithelial, stromal and luminal composition of the tissue was determined using a computer-assisted method for quantitative morphometric analysis. Apoptosis was detected as the apoptotic index (AI) using the TdT dUTP nick-end labelling assay. Cell proliferation was determined as the proliferation index (PI) using Ki-67 immunostaining. The expression of epidermal growth factor receptor (EGFR), transforming growth factor beta1 (TGFbeta1), androgen receptor (AR) and bcl-2 were assessed immunohistochemically.
• Results: There was no difference in the stroma/epithelium ratio between PZ and TZ hyperplastic nodules (P > 0.05). The mean AI in epithelium was almost identical to the corresponding PI. In stroma, no apoptotic cells were detectable. There was a significantly higher PI and AI in the glandular epithelial cells in PZ hyperplastic than in TZ hyperplastic nodules, but no difference in PI of the stromal cells between PZ and TZ hyperplastic nodules. There was significantly higher expression of TGFbeta1 and lower expression of EGFR and bcl-2 in PZ than TZ hyperplastic nodules (P < 0.05). There was no difference in AR expression between PZ and TZ hyperplastic nodules (P > 0.05).
• Conclusions: These results indicate that some hyperplastic nodules in PZ might originate from the PZ, and the formation of these nodules might be modulated in a different way from that in the TZ.
  
  
• Editorial Comment
  It is well accepted that benign prostatic hyperplasia (BPH) develops from the transition zone (TZ) and from the periurethral glans, while carcinoma originates from the peripheral zone (PZ). Nevertheless, previous studies, including studies by that same group, reported that hypoechoic lesions in the PZ can be found as BPH histologically. Some authors suggested that the hyperplastic nodules in the PZ might be exophytic BPH in the TZ or the migration of ectopic TZ tissue into the PZ. The authors of the present study speculate that it is more likely that the hyperplastic nodules might originate from the PZ.
  In the present study, the epithelial, stromal and luminal composition of the tissue was determined using a computer-assisted quantitative morphometric analysis method in biopsy specimens obtained from patients with PZ or TZ hypoechoic nodules on transrectal ultrasound, and that were histologically confirmed as BPH. The incidence of apoptosis and cell proliferation was analyzed comparatively in these hypoechoic nodules according to the zonal location. The authors also examined the relative expression of proteins involved in the regulation of prostate proliferation and apoptosis: (i) epidermal growth factor receptor (EGFR), which is in the signal transduction pathway that participates in the mediation of cell growth and has been implicated in prostatic epithelia cell proliferation in vitro; (ii) TGFb1, the most extensively studied negative growth factor. The predominant effect of TGFb1 on growth in vivo and in vitro is inhibition of cell proliferation; (iii) bcl-2, a potent apoptosis suppressor; and (iv) androgen receptor (AR); steroid binding to AR could stimulate proliferation and differentiation of epithelial cells and inhibit prostate cell apoptosis.
  The results of the present study showed that no apoptotic cells were detectable in stroma, which indicated stromal growth due to cell proliferation, in the absence of cell death. The authors discussed that recent studies reported that the cell apoptotic rate in different regions of the ductal system is different, apoptosis being much less in the proximal ends. The proximal and distal regions of the ductal system correspond to the TZ and PZ of the human prostate. The present results showed that the cell apoptotic rate in the epithelium was much higher in PZ than in TZ hyperplastic nodules, which was in concordance with the higher TGF 1 and lower bcl-2 expression in the epithelium of PZ than TZ hyperplastic nodules. In the present study, TGFb1 staining was intense in the epithelial cells, and bcl-2 expression was consistently restricted to the basal cell layer. This might explain why no apoptotic cells were detectable in the stroma of PZ and TZ hyperplastic nodules.
  So, the authors concluded that the present results indicate that some hyperplastic nodules in the PZ might originate from the PZ, and the formation of these nodules might be modulated in a different way to that in the TZ.

Dr. Francisco J.B. Sampaio
Full-Professor and Chair, Urogenital Research Unit
State University of Rio de Janeiro
Rio de Janeiro, RJ, Brazil
E-mail: sampaio@urogenitalresearch.org