An immunohistochemical assessment of hypoxia in prostate carcinoma using pimonidazole: Implications for radioresistance

Purpose: To investigate the presence of hypoxia in human prostate carcinoma by using pimonidazole immunohistochemical labeling in radical prostatectomy specimens.

Methods and Materials: Forty-three patients (median age, 69 years; range, 49–83 years) with localized prostate adenocarcinoma received 0.5 gm/m² i.v. pimonidazole 16–24 h before radical prostatectomy. Hypoxia was detected with a monoclonal antibody directed against pimonidazole and scored in formalin-fixed, paraffin-embedded sections. Median and maximal vessel counts were measured with CD34.

Results: Thirty-seven patients completed the study. Pimonidazole binding was present in prostate carcinomas in 34 of 37 patients (92%) and in benign prostatic hyperplasia in 35 of 37 patients (95%). A positive correlation of 3+ pimonidazole binding with Gleason score was demonstrated (Spearman’s rank, p = 0.044). Vascularity scores did not correlate with hypoxic status or clinical prognostic parameters.

Conclusion: Prostate carcinoma and benign prostatic hyperplasia have significant areas of hypoxia; greater hypoxia scores are seen with more aggressive prostate cancer. It is postulated that a hypoxic microenvironment within the prostate might be responsible for the promotion of secondary genetic alterations and angiogenic stimulation, leading to malignant progression, a more aggressive cell phenotype, and greater radioresistance. Modification of radiation regimens to specifically target hypoxia might improve local tumor control.

Keywords:  Prostate carcinoma , Pimonidazole , Hypoxia , Radioresistance