p53 ACCUMULATION ASSOCIATED WITH bcl-2, THE PROLIFERATION MARKER MIB-1 AND SURVIVAL IN PATIENTS WITH PROSTATE CANCER SUBJECTED TO WATCHFUL WAITING

PURPOSE: We describe the association of p53 nuclear protein accumulation with bcl-2 expression, tumor cell proliferation and clinical outcome in a prostate cancer population undergoing watchful waiting. MATERIALS AND METHODS: Immunohistochemical staining for p53 was semiquantitatively scored in archival formalin fixed, paraffin embedded tumor tissue obtained at diagnosis in 221 patients with prostate cancer. At a median of 15 years followup was nearly complete. Eventually 57% of the patients died of prostate cancer. RESULTS: p53 Immunohistochemical staining was heterogeneous but in all cases at least clusters of tumor cells had nuclear staining for p53. The percent of p53 immunoreactive tumor cells was scored as 0 to 4+ in p53 positive hot spots. p53 immunoreactivity correlated with clinical stage and histopathological grade (p = 0.003 and 0.009, respectively). When dichotomized into low (0% to 50%) and high (51% to 100%) immunoreactivity groups of 40 and 181 patients, respectively, p53 accumulation was significantly associated with disease specific survival in the study population overall (p <0. 0001) and in the 125 with clinically localized disease (p = 0.0002). p53 Immunoreactivity was significantly (p <0.001) associated with the proliferation marker MIB-1 (median value 10.3, range 0 to 46.1) but insignificantly (p = 0.8) correlated with bcl-2 expression (52% positive). However, patients with combined favorable MIB-1 and bcl-2 status were stratified into significant (p = 0.02) prognostic groups by p53 immunohistochemical status. Multivariate analysis revealed that p53 immunoreactivity was a significant prognostic factor in patients with clinically localized prostate cancer (p <0.0001). CONCLUSIONS: p53 Nuclear protein accumulation detected by immunohistochemical study was an independent adverse prognostic factor in patients with prostate cancer undergoing watchful waiting.