TY - JOUR
T1 - p53 nuclear accumulation as an early indicator of lethal prostate cancer
AU - Quinn, David I.
AU - Stricker, Phillip D.
AU - Kench, James G.
AU - Grogan, Judith
AU - Haynes, Anne Maree
AU - Henshall, Susan M.
AU - Grygiel, John J.
AU - Delprado, Warick
AU - Turner, Jennifer J.
AU - Horvath, Lisa G.
AU - Mahon, Kate L.
PY - 2019/10/1
Y1 - 2019/10/1
N2 - Background: 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. Methods: 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. Results: 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. Conclusions: p53 aberrations in radical prostatectomy tissue predict clinically relevant endpoints of MR and PCSM.
AB - Background: 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. Methods: 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. Results: 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. Conclusions: p53 aberrations in radical prostatectomy tissue predict clinically relevant endpoints of MR and PCSM.
UR - http://www.scopus.com/inward/record.url?scp=85070937050&partnerID=8YFLogxK
U2 - 10.1038/s41416-019-0549-8
DO - 10.1038/s41416-019-0549-8
M3 - Article
C2 - 31409910
AN - SCOPUS:85070937050
SN - 0007-0920
VL - 121
SP - 578
EP - 583
JO - British Journal of Cancer
JF - British Journal of Cancer
IS - 7
ER -