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p53 nuclear accumulation as an early indicator of lethal prostate cancer


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 x200 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.

Type Journal
ISBN 0007-0920
Authors Quinn, D. I.; Stricker, P. D.; Kench, J. G.; Grogan, J.; Haynes, A. M.; Henshall, S. M.; Grygiel, J. J.; Delprado, W.; Turner, J. J.; Horvath, L. G.; Mahon, K. L.
Responsible Garvan Author A/Prof Lisa Horvath
Publisher Name British Journal of Cancer
Published Date 2019-10-31
Published Volume 121
Published Issue 7
Published Pages 578-583
Status Published in-print
DOI 10.1038/s41416-019-0549-8
URL link to publisher's version