p53 nuclear accumulation as an early indicator of lethal prostate cancer.

Autor: Quinn DI; Norris Comprehensive Cancer Centre, University of Southern California, Los Angeles, USA., Stricker PD; St Vincents Prostate Cancer Centre, Sydney, Australia., Kench JG; Garvan Institute of Medical Research, Sydney, Australia.; Royal Prince Alfred Hospital, Sydney, Australia.; University of Sydney, Sydney, Australia., Grogan J; Garvan Institute of Medical Research, Sydney, Australia., Haynes AM; Garvan Institute of Medical Research, Sydney, Australia., Henshall SM; Union for International Cancer Control, Geneva, Switzerland., Grygiel JJ; St Vincents Hospital, Sydney, Australia., Delprado W; Douglass Hanly Moir Pathology, Sydney, Australia., Turner JJ; Douglass Hanly Moir Pathology, Sydney, Australia., Horvath LG; Garvan Institute of Medical Research, Sydney, Australia.; Royal Prince Alfred Hospital, Sydney, Australia.; University of Sydney, Sydney, Australia.; Chris O'Brien Lifehouse, Sydney, Australia., Mahon KL; Garvan Institute of Medical Research, Sydney, Australia. kate.mahon@lh.org.au.; Royal Prince Alfred Hospital, Sydney, Australia. kate.mahon@lh.org.au.; University of Sydney, Sydney, Australia. kate.mahon@lh.org.au.; Chris O'Brien Lifehouse, Sydney, Australia. kate.mahon@lh.org.au.
Jazyk: angličtina
Zdroj: British journal of cancer [Br J Cancer] 2019 Oct; Vol. 121 (7), pp. 578-583. Date of Electronic Publication: 2019 Aug 14.
DOI: 10.1038/s41416-019-0549-8
Abstrakt: 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.
Databáze: MEDLINE
Externí odkaz: