Open AccessA three‐protein biomarker panel assessed in diagnostic tissue predicts death from prostate cancer for men with localized disease
Author(s) -
Severi Gianluca,
FitzGerald Liesel M.,
Muller David C.,
Pedersen John,
Longano Anthony,
Southey Melissa C.,
Hopper John L.,
English Dallas R.,
Giles Graham G.,
Mills John
Publication year - 2014
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.281
Subject(s) - prostate cancer , medicine , oncology , cancer , prostate , disease , biomarker , cause of death , epidemiology , stage (stratigraphy) , pathology , biology , paleontology , biochemistry
Abstract Only a minority of prostate cancers lead to death. Because no tissue biomarkers of aggressiveness other than Gleason score are available at diagnosis, many nonlethal cancers are treated aggressively. We evaluated whether a panel of biomarkers, associated with a range of disease outcomes in previous studies, could predict death from prostate cancer for men with localized disease. Using a case‐only design, subjects were identified from three Australian epidemiological studies. Men who had died of their disease, “cases” ( N = 83), were matched to “referents” ( N = 232), those who had not died of prostate cancer, using incidence density sampling. Diagnostic tissue was retrieved to assess expression of AZGP 1, MUC 1, NKX 3.1, p53, and PTEN by semiquantitative immunohistochemistry (IHC). Poisson regression was used to estimate mortality rate ratios ( MRR s) adjusted for age, Gleason score, and stage and to estimate survival probabilities. Expression of MUC 1 and p53 was associated with increased mortality ( MRR 2.51, 95% CI 1.14–5.54, P = 0.02 and 3.08, 95% CI 1.41–6.95, P = 0.005, respectively), whereas AZGP 1 expression was associated with decreased mortality ( MRR 0.44, 95% CI 0.20–0.96, P = 0.04). Analyzing all markers under a combined model indicated that the three markers were independent predictors of prostate cancer death and survival. For men with localized disease at diagnosis, assessment of AZGP 1, MUC 1, and p53 expression in diagnostic tissue by IHC could potentially improve estimates of risk of dying from prostate cancer based only on Gleason score and clinical stage.