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

ObjectivesTo 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).MethodsA 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.ResultsThe 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.ConclusionsThe development of BPH may be associated with both stromal growth due to active stromal cell proliferation and epithelial growth due to reduced glandular apoptosis.