PROTEIN EXPRESSION OF P53, BCL-2, AND KI-67 (MIB-1) AS PROGNOSTIC BIOMARKERS IN PATIENTS WITH SURGICALLY TREATED, CLINICALLY LOCALIZED PROSTATE-CANCER

Background. Protein expression in the primary tumor of the tumor suppr essor gene p53 and the proto-oncogene bcl-2 have been shown to lie pro gnostic biomarkers of cancer recurrence after radical prostatectomy in patients with clinically localized prostate cancer. Cancer cell Proli feration as measured by immunohistochemical markers such as the MIB-1 antibody for Ki-67 has recently been suggested to be of prognostic val ue in prostate cancer. The goal of this study was to determine the cli nical use of p53, Ki-67 (MIB-1), and bcl-2 immunohistochemical protein expression in the primary tumor as combined predictors of disease pro gression after radical prostatectomy (RP). Methods. Protein expression s of p53, Ki-67, and bcl-2 were evaluated in archival paraffin-embedde d RP specimens from 162 patients monitored from 1 to 10 years (mean, 4 .5 years) and correlated to stage, grade, race, and serologic (prostat e-specific antigen) recurrence after operation. Results. Expression wa s defected in 112 (69.1%), 44 (27.2%), and 62 (38.3%) of 162 patients for p53 (1+ or greater), bcl-2 (1+ or greater), and Ki-67 (2+ or great er), respectively. Biomarker expressions were not correlated to age an d race; however, all increased with increasing stage and grade. The de gree Of expression by percentage of malignant cells staining correlate d to recurrence for p53 and Ki-67 but nob for bcl-2. All three markers were correlated to raw and Kaplan-Meier recurrence by means of univar iate analysis with recurrence estimates at 6 years of 60.7% versus 24. 2%, 84.2% versus 38.6%, and 72.4% versus 30.6% comparing positive vers us negative expression of p53, bcl-2, and Ki-67, respectively. p53 and bcl-2 remained as independent prognostic markers by Cox multivariate regression analysis. Although Ki-67 did not remain an independent mark er, it added prognostic use in certain subsets of patients. Conclusion s. p53 bcl-2, and Ki-67 (MIB-1) appear to be important biomarkers to P redict recurrence in patients with clinically localized prostate cance r after RP, and all three biomarkers deserve further study.