p53 nuclear accumulation as an early indicator of lethal prostate cancer

After radical prostatectomy (RP) for prostate cancer (PC), p53 alterations predict biochemical relapse (BCR), however, recent evidence suggests that metastatic relapse (MR) not BCR is a surrogate for PC specific mortality (PCSM). This updated analysis of a previously published study investigated the association between p53 aberrations, MR and PCSM in men with localised PC. Two hundred and seventy-one men with localised PC treated with RP were included. RP specimens stained for p53 by immunohistochemistry were scored as (a) percentage of p53-positive tumour nuclei; and (b) clustering, where ≥12 p53-positive cells within a ×200 power field was deemed ‘cluster positive’. Associations between p53 status and clinical outcomes (BCR, MR and PCSM) were evaluated. Increasing percentage of p53-positive nuclei was significantly associated with shorter time to BCR, MR and PCSM (All p < 0.001). Half of the patients were p53 cluster positive. p53 cluster positivity was significantly associated with poorer outcomes at all clinical endpoints (BCR: HR 2.0, 95% CI 1.51–2.65, p < 0.001; MR: HR 4.1, 95% CI 2.02–8.14, p < 0.001; PCSM: HR 12.2, 95% CI 1.6–93; p = 0.016). These associations were independent of other established prognostic variables. p53 aberrations in radical prostatectomy tissue predict clinically relevant endpoints of MR and PCSM.