Elsevier

Urology

Volume 68, Issue 4, October 2006, Pages 905-910
Urology

Basic science
Apoptosis profiles in benign prostatic hyperplasia: Close associations of cell kinetics with percent area density of histologic composition

https://doi.org/10.1016/j.urology.2006.05.013Get rights and content

Abstract

Objectives

To investigate the possible correlations of apoptosis and apoptosis-associated factors, including the apoptotic index (AI), proliferation index (PI), and expression of Bcl-2 and caspase 3, with the percent area density of epithelium and stroma in benign prostatic hyperplasia (BPH).

Methods

A total of 60 patients with histologically determined BPH were investigated. The percent area density of epithelium and stroma was determined using a computerized image analysis system after Masson’s trichrome staining. Apoptosis was detected using the AI through the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling assay. Cell proliferation was determined using the PI through Ki-67 immunostaining. The expression of Bcl-2 and caspase 3 was immunohistochemically examined. Double-label immunofluorescent staining was performed to assess co-localization of Bcl-2 and caspase 3.

Results

The stroma/epithelium ratio ranged from 4.6 to 6.3 (average 5.2) in BPH. A greater stromal PI was closely related to the percent area density of stroma (P <0.01), and a greater epithelial AI was reversely related to the percent area density of the epithelium (P <0.05). Bcl-2 and caspase 3 expression was detected in 50 (80%) and 48 (75%) of 60 BPH samples, respectively. The expression of Bcl-2 and caspase 3 was not related to PI, AI, or the percent area density of the BPH components (P >0.05). Immunofluorescence analysis revealed co-localization of Bcl-2 and caspase 3 in the serial sections of BPH specimens that already showed either Bcl-2 or caspase 3 expression.

Conclusions

The development of BPH may be associated with both stromal growth due to active stromal cell proliferation and epithelial growth due to reduced glandular apoptosis.

Section snippets

Material and methods

This study included 60 patients with BPH who underwent transurethral resection of the prostate or suprapubic prostatectomy. Their age range was 59 to 76 years (median age 66). None of these patients had undergone previous hormonal manipulation. The formalin-fixed and paraffin-embedded specimens were cut into 5-μm-thick sections and placed on Poly-l-lysine-treated glass slides. For histopathologic examination, each paraffin block was step sectioned and routinely stained with hematoxylin-eosin

Percent Area Density

The average percent area density of epithelium, stroma, and lumen was 14.4% ± 4.1%, 75.5% ± 10.7%, and 10.1% ± 5.9 %, respectively. The ratio of stroma to epithelium ranged from 4.6:1 to 6.3:1 (average 5.2:1) in BPH specimens. The percent area density of epithelium and stroma was not related to patient age or prostate volume.

Apoptotic and Proliferation Indexes

Both TUNEL-positive cells and Ki-67-positive cells were detected in the glandular cells and stromal cells of BPH (Fig. 1A,B). The average PI and AI were 1.8 and 0.7 in the

Comment

It is known that human BPH is the result of proliferation of the stromal and epithelial compartments. This proliferation begins in the stroma, with proliferation of the glandular epithelium secondarily induced.1 A number of studies have shown close associations between the development and severity of clinical BPH and the cellular composition of the prostate.17, 18 It is clear that the proportion of stromal components is absolutely greater than that of epithelial compartments in human BPH.

Conclusions

This is the first study to examine correlations of apoptosis and apoptosis-associated factors with the percent area density of epithelial and stromal components in BPH. Our data showed a close relation of a greater PI to the percent area density of stroma and an inverse relation of a greater AI to the percent area density of epithelium in BPH tissue. The development of BPH may be associated with both stromal growth, due to active mesenchymal-stromal cell proliferation, and epithelial growth,

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