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

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.