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Abstract: The aim of this study was to investigate the expression of p21waf1/cip1, p27kip1, p63 and androgen receptor proteins in relation to serum prostate specific antigen levels in low and high Gleason score prostate cancers. Biopsies of patients suffering from prostate adenocarcinoma of low (3 + 3 to 3 + 4) and high (5 + 4 to 5 + 5) Gleason scores (13 cases each group) were immunostained for positive regulators of cell cycle control (p21waf1/cip1 and p27kip1), and essential markers of normal prostate gland ontogeny (p63) and growth (androgen receptor) to find differentially expressed markers of malignant progression. Serum prostate specific antigen levels were also monitored at the time of biopsy and following anti-androgen therapy. All cases except one in each group were androgen receptor positive. P63 and p21waf1/cip1 proteins detected in normal basal cell nuclei were lost in all but one studied tumors respectively. P27kip1 protein, however, was detected in all low Gleason score prostate cancers, but it was found in only 7/13 high score cases. Prostate specific antigen levels, either pre- or post-treatment, did not show strict correlation with the p27kip1 results. The low to high grade dedifferentiation of prostate adenocarcinoma is accompanied with the down-regulation of p27kip1 protein, which may be an important molecular sign of the lost cell cycle control.