Preoperative p53, bcl-2, CD44 and E-cadherin immunohistochemistry as predictors of biochemical relapse after radical prostatectomy

Purpose: Since radical prostatectomy is performed to cure prostate cancer, identification of markers enabling preoperative prediction of relapse after radical prostatectomy is essential to counsel and select patients for adju vant therapy. Aberrant p53, bcl-2, CD44 and E-cadherin immunohistochemistry has been associated with aggressiveness in prostate cancer. We assessed th ese biomarkers in biopsy and radical prostatectomy specimens as predictors of biochemical relapse. Materials and Methods: A total of 76 patients with untreated clinically loc alized prostatic adenocarcinoma underwent radical prostatectomy. Preoperati ve (prostate specific antigen, biopsy Gleason score) and postoperative (pat hological stage and margin status) variables, biopsy and radical prostatect omy biomarker immunohistochemistry were correlated with relapse. Univariate and multivariate statistical analyses identified significant predictors. Results: Of the 76 patients 23 (30%) had relapse (mean followup 38 months). Aberrant p53, bcl-2, CD44 and E-cadherin expression was observed in 64, 12 , 85 and 12% of biopsies and 57, 20, 64 and 49% of radical prostatectomy sp ecimens, respectively. Biopsy Gleason 7 to 10 and biopsy p53, respectively, gave the highest positive and negative predictive values for relapse. Rela pse occurred in 13% of patients with normal biopsy p53 and in half with abe rrant p53. Multivariate analysis revealed Gleason score and p53 to be indep endent preoperative predictors (p = 0.01 and 0.02, respectively). Estimated risk of relapse was 3.5 times higher in patients with Gleason scores 7 to 10 and 24% higher in those with aberrant p53. Significant postoperative pre dictors were bcl-2, p53, Gleason score and margin status (p = 0.01, 0.01, 0 .04 and 0.01, respectively). Conclusions: Aberrant biopsy p53 is associated with a significantly worse o utcome after radical prostatectomy than normal p53, highlighting a potentia l clinical role for p53. Postoperative p53 and bcl-2 were significant predi ctors of outcome after radical prostatectomy.