TY - JOUR
T1 - A three-protein biomarker panel assessed in diagnostic tissue predicts death from prostate cancer for men with localized disease
AU - Severi, Gianluca
AU - Fitzgerald, Liesel M.
AU - Muller, David C.
AU - Pedersen, John
AU - Longano, Anthony
AU - Southey, Melissa C.
AU - Hopper, John L.
AU - English, Dallas R.
AU - Giles, Graham G.
AU - Mills, John
N1 - Publisher Copyright:
© 2014 The Authors.
PY - 2014/10/1
Y1 - 2014/10/1
N2 - 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. We evaluated whether a panel of biomarkers (AZGP1, MUC1, NKX3.1, p53, and PTEN), assessed by immunohistochemistry on diagnostic tissue, could predict death from prostate cancer in men with localized disease. Expression of MUC1 and p53 was associated with increased mortality (MRR 2.51 and 3.08, P < 0.03), whereas AZGP1 expression was associated with decreased mortality (MRR 0.44, P = 0.04). For men with localized disease at diagnosis, assessing the expression of these three proteins in diagnostic tissue could potentially improve estimates of risk of dying from prostate cancer based only on Gleason score and clinical stage.
AB - 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. We evaluated whether a panel of biomarkers (AZGP1, MUC1, NKX3.1, p53, and PTEN), assessed by immunohistochemistry on diagnostic tissue, could predict death from prostate cancer in men with localized disease. Expression of MUC1 and p53 was associated with increased mortality (MRR 2.51 and 3.08, P < 0.03), whereas AZGP1 expression was associated with decreased mortality (MRR 0.44, P = 0.04). For men with localized disease at diagnosis, assessing the expression of these three proteins in diagnostic tissue could potentially improve estimates of risk of dying from prostate cancer based only on Gleason score and clinical stage.
KW - AZGP1
KW - Immunohistochemistry
KW - MUC1
KW - NKX3.1
KW - P53
KW - Prognostic markers
KW - Prostate cancer-specific death
UR - http://www.scopus.com/inward/record.url?scp=84991506022&partnerID=8YFLogxK
U2 - 10.1002/cam4.281
DO - 10.1002/cam4.281
M3 - Article
C2 - 24909936
AN - SCOPUS:84991506022
SN - 2045-7634
VL - 3
SP - 1266
EP - 1274
JO - Cancer Medicine
JF - Cancer Medicine
IS - 5
ER -