Prognostic value of cell cycle proteins p27(kip1) and MIB-1, and the cell adhesion protein CD44s in surgically treated patients with prostate cancer

Purpose: Molecular tissue markers may give the clinician additional informa tion about patients with prostate cancer at risk for treatment failure afte r retropubic radical prostatectomy. We substantiate the prognostic value of 3 tissue markers, the cell cycle proteins p27(kip1) and MIB-1, and the cel l adhesion protein CD44s, in addition to more conventional pathological pro gnosticators in an historical (before prostate specific antigen) cohort of patients with prostate cancer. Materials and Methods: Representative tumor sections from 92 patients who u nderwent retropubic radical prostatectomy were immunohistochemically staine d with antibodies against p27(kip1), MIB-1 (Ki-67) and CD44s, and assessed in a semiquantitative manner. Gleason score and pathological tumor stage we re recorded. All variables were correlated with clinical progression and di sease specific survival on univariate and multivariate analyses. Results: On univariate analysis low (less than 50%) p27(kip1), high (10% or greater) MIB-1 and loss of CD44s expression were significantly associated with clinical outcome parameters, although MIB-1 did not reach statistical significance for disease specific survival. All 3 molecules were highly cor related with Gleason score and pathological tumor stage. Multivariate analy sis showed that low p27(kip1) was independent of grade and stage in predict ing clinical recurrence (p < 0.001) and disease specific survival (p = 0.04 5), while loss of CD44s was an additional independent prognostic factor for clinical recurrence (p = 0.02). Conclusions: Reduced p27(kip1) expression is an independent predictor of po or outcome in prostate cancer, while MIB-1 is not. Decreased expression of CD44s yields additional information in predicting clinical recurrence. Thes e tissue markers may identify patients at risk for disease recurrence after retropubic radical prostatectomy who may benefit from adjuvant therapy.