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. 2019 Oct;121(7):578-583.
doi: 10.1038/s41416-019-0549-8. Epub 2019 Aug 14.

p53 nuclear accumulation as an early indicator of lethal prostate cancer

David I Quinn  1 , Phillip D Stricker  2 , James G Kench  3   4   5 , Judith Grogan  3 , Anne-Maree Haynes  3 , Susan M Henshall  6 , John J Grygiel  7 , Warick Delprado  8 , Jennifer J Turner  8 , Lisa G Horvath #  3   4   5   9 , Kate L Mahon #  10   11   12   13
Affiliations

p53 nuclear accumulation as an early indicator of lethal prostate cancer

David I Quinn et al. Br J Cancer. 2019 Oct.

Abstract

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.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Kaplan–Meier analysis of nuclear p53 score strata for a biochemical progression-free survival, b metastasis-free survival, c prostate cancer specific survival
Fig. 2
Fig. 2
Kaplan–Meier analysis of nuclear p53 cluster status for a biochemical progression-free survival, b metastasis-free survival, c prostate cancer specific survival
See this image and copyright information in PMC

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