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


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.
Borre
M
M
Danish Cancer Society, Department of Experimental Clinical Oncology and Urology, Aarhus University Hospital, Denmark.
Stausbol-Gron
B
B
Overgaard
J
J
D000368:Aged; D000369:Aged, 80 and over; D034961:Antigens, Nuclear; D014408:Biomarkers, Tumor / Q000032:analysis*; D002423:Cause of Death; D002455:Cell Division; D004268:DNA-Binding Proteins / Q000032:analysis*; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000032:analysis*; D011379:Prognosis; D016016:Proportional Hazards Models; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis*; D015996:Survival Rate; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*
D034961:Antigens, Nuclear; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D019394:Ki-67 Antigen; D009687:Nuclear Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53