title: A three-protein biomarker panel assessed in diagnostic tissue predicts death from prostate cancer for men with localized disease.
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 AZGP1, MUC1, NKX3.1, p53, and PTEN by semiquantitative immunohistochemistry (IHC). Poisson regression was used to estimate mortality rate ratios (MRRs) adjusted for age, Gleason score, and stage and to estimate survival probabilities. Expression of MUC1 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 AZGP1 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 AZGP1, MUC1, 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.
authors.affiliation: Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Victoria, 3004, Australia; Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, School of Population Health, The University of Melbourne, Melbourne, Victoria, 3010, Australia.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Severi
authors.forename: Liesel M
authors.initials: LM
authors.lastname: FitzGerald
authors.forename: David C
authors.initials: DC
authors.lastname: Muller
authors.forename: John
authors.initials: J
authors.lastname: Pedersen
authors.forename: Anthony
authors.initials: A
authors.lastname: Longano
authors.forename: Melissa C
authors.initials: MC
authors.lastname: Southey
authors.forename: John L
authors.initials: JL
authors.lastname: Hopper
authors.forename: Dallas R
authors.initials: DR
authors.lastname: English
authors.forename: Graham G
authors.initials: GG
authors.lastname: Giles
authors.forename: John
authors.initials: J
authors.lastname: Mills
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism; D016022:Case-Control Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000378:metabolism* / Q000401:mortality
chemical_list: D015415:Biomarkers; D014408:Biomarkers, Tumor
keywords: AZGP1; MUC1; NKX3.1; immunohistochemistry; p53; prognostic markers; prostate cancer-specific death