The prognostic value of the cell cycle proteins p27/Kip1 and Ki67/MIB1 immunohistochemical expression in patients with surgically treated localized prostate cancer

Abstract

4686 Background: The assessment of the cyclin-dependent kinase inhibitor p27/Kip1 & the cell proliferation marker Ki67/MIB1 immunohistochemical (IHC) expression (E) as predictive indicators of prostate cancer (PC) biochemical failure (BF) after radical prostatectomy (RP). Methods: Included in the study were 130 consecutive patients - median age 66 (47–76) years & with median preoperative serum PSA 9.23 (2.5–45) ng/ml - who underwent RP for localized PC, between 01/1994 & 12/2001. Follow-up information was available for 94 patients. The median follow-up period was 28 (1–97) months. A cutoff value of 0.2 ng/ml of serum PSA was established as a BF threshold. The IHC method of streptavidin biotin peroxidase was performed on paraffin tissue sections, using antibodies against p27/Kip1 & Ki67/MIB1. Results: A statistically significant inverse correlation was observed between p27/Kip1 IHCE & (i) seminal vesicles invasion (SVI) [P=0.009], (ii) tumor volume [P=0.025] & (iii) preoperative serum PSA [P=0.002]. A statistically significant positive correlation was observed between Ki67/MIB1 IHCE & pelvic lymph nodes metastasis (PLNM) [P=0.006]. No statistically significant correlation was found between the studied markers & Gleason score (GS), periprostatic tissue infiltration (PTI), surgical margins infiltration, the presence of PIN & prostate weight. BF was observed in 35/94 (37%) patients. Kaplan-Meier survival curves showed that low p27/Kip1 & high Ki67/MIB1 IHCE, as well as the synchronous IHCE of low p27/Kip1 & high Ki67/MIB1 were significant predictors of BF (P=0.0005, P=0.0040 & P=0.0011 respectively). GS, PTI, SVI & PLNM were significant predictors for BF as well (P=0.044, P=0.001, P=0.000 & P=0.005 respectively). However, in the multivariate analysis (Cox Regression) SVI, PLNM & MIB1 IHCE were the only independent prognostic factors for BF (P=0.001, P=0.007 & P=0.020 respectively). Conclusions: The cell proliferation index assessed by Ki67/MIB1 IHCE may be a useful marker for BF prediction & decision management in patients with clinically localized PC after RP. No significant financial relationships to disclose.