p53 accumulation associated with bcl-2, the proliferation marker MIB-1 andsurvival in patients with prostate cancer subjected to watchful waiting

Purpose: We describe the association of p53 nuclear protein accumulation wi th bcl-2 expression, tumor cell proliferation and clinical outcome in a pro state cancer population undergoing watchful waiting. Materials and Methods: Immunohistochemical staining for p53 was semiquantit atively scored in archival formalin fixed, paraffin embedded tumor tissue o btained at diagnosis in 221 patients with prostate cancer. At a median of 1 5 years followup was nearly complete. Eventually 57% of the patients died o f prostate cancer. Results: p53 Immunohistochemical staining was heterogeneous but in all case s at least clusters of tumor cells had nuclear staining for p53. The percen t of p53 immunoreactive tumor cells was scored as 0 to 4+ in p53 positive h ot spots, p53 immunoreactivity correlated with clinical stage and histopath ological 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 18 1 patients, respectively, p53 accumulation was significantly associated wit h disease specific survival in the study population overall (p <0.0001) and in the 125 with clinically localized disease (p = 0.0002). p53 Immunoreact ivity 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) c orrelated with bcl-2 expression (52% positive). However, patients with comb ined favorable MIB-1 and bcl-2 status were stratified into significant (p = 0.02) prognostic groups by p53 immunohistochemical status. Multivariate an alysis revealed that p53 immunoreactivity was a significant prognostic fact or in patients with clinically localized prostate cancer (p <0.0001). Conclusions: p53 Nuclear protein accumulation detected by immunohistochemic al study was an independent adverse prognostic factor in patients with pros tate cancer undergoing watchful waiting.