TY - JOUR
T1 - Loss of PTEN expression is associated with increased risk of recurrence after prostatectomy for clinically localized prostate cancer
AU - Chaux, Alcides
AU - Peskoe, Sarah B.
AU - Gonzalez-Roibon, Nilda
AU - Schultz, Luciana
AU - Albadine, Roula
AU - Hicks, Jessica
AU - De Marzo, Angelo M.
AU - Platz, Elizabeth A.
AU - Netto, George J.
N1 - Funding Information:
This study was partially supported by the Johns Hopkins Medicine–Patana Fund for Research, NIH-NCI P50 CA58236 Grant–Johns Hopkins University SPORE in Prostate Cancer, and the Patrick C Walsh Research Fund. Dr Alcides Chaux was partially supported by an award granted by the Consejo Nacional de Ciencia y Tecnologia, CON-ACYT (National Council of Science and Technology) dependent of the Presidency of the Republic of Paraguay, as an Active Researcher of Level 1 of the Programa Nacional de Incentivo a los Investiga-dores, PRONII (National Incentive Program for Researchers).
Funding Information:
We acknowledge the contributions of Helen L. Fedor from the Brady Urological Research Institute Prostate Specimen Repository at the Johns Hopkins School of Medicine for the generation of the TMAs for this nested case–control study, funded in part by the Prostate SPORE Pathology Core (P50 CA58236) and a DOD grant (DAMD 17-03-0273).
PY - 2012/11
Y1 - 2012/11
N2 - PTEN (phosphatase and tensin homolog on chromosome 10) is one of the most frequently lost tumor suppressor genes in human cancers and it has been described in more than two-thirds of patients with advanced/aggressive prostate cancer. Previous studies suggest that, in prostate cancer, genomic PTEN loss is associated with tumor progression and poor prognosis. Thus, we evaluated whether immunohistochemical PTEN expression in prostate cancer glands was associated with higher risk of recurrence, using a nested casecontrol study that included 451 men who recurred and 451 men who did not recur with clinically localized prostate cancer treated by radical prostatectomy. Recurrence was defined as biochemical recurrence (serum prostate-specific antigen >0.2 ng/ml) or clinical recurrence (local recurrence, systemic metastases, or prostate cancer-related death). Cases and controls were matched on pathological T stage, Gleason score, race/ethnicity, and age at surgery. Odds ratios of recurrence and 95% confidence intervals were estimated using conditional logistic regression to account for the matching factors and to adjust for year of surgery, preoperative prostate-specific antigen concentrations, and status of surgical margins. Men who recurred had a higher proportion of PTEN negative expression (16 vs 11%, P0.05) and PTEN loss (40 vs 31%, P0.02) than controls. Men with markedly decreased PTEN staining had a higher risk of recurrence (odds ratio1.67; 95% confidence intervals 1.09, 2.57; P0.02) when compared with all other men. In summary, in patients with clinically localized prostate cancer treated by prostatectomy, decreased PTEN expression was associated with an increased risk of recurrence, independent of known clinicopathological factors.
AB - PTEN (phosphatase and tensin homolog on chromosome 10) is one of the most frequently lost tumor suppressor genes in human cancers and it has been described in more than two-thirds of patients with advanced/aggressive prostate cancer. Previous studies suggest that, in prostate cancer, genomic PTEN loss is associated with tumor progression and poor prognosis. Thus, we evaluated whether immunohistochemical PTEN expression in prostate cancer glands was associated with higher risk of recurrence, using a nested casecontrol study that included 451 men who recurred and 451 men who did not recur with clinically localized prostate cancer treated by radical prostatectomy. Recurrence was defined as biochemical recurrence (serum prostate-specific antigen >0.2 ng/ml) or clinical recurrence (local recurrence, systemic metastases, or prostate cancer-related death). Cases and controls were matched on pathological T stage, Gleason score, race/ethnicity, and age at surgery. Odds ratios of recurrence and 95% confidence intervals were estimated using conditional logistic regression to account for the matching factors and to adjust for year of surgery, preoperative prostate-specific antigen concentrations, and status of surgical margins. Men who recurred had a higher proportion of PTEN negative expression (16 vs 11%, P0.05) and PTEN loss (40 vs 31%, P0.02) than controls. Men with markedly decreased PTEN staining had a higher risk of recurrence (odds ratio1.67; 95% confidence intervals 1.09, 2.57; P0.02) when compared with all other men. In summary, in patients with clinically localized prostate cancer treated by prostatectomy, decreased PTEN expression was associated with an increased risk of recurrence, independent of known clinicopathological factors.
KW - PTEN
KW - biochemical recurrence
KW - death
KW - immunohistochemistry
KW - metastasis
KW - prognosis
KW - prostate cancer
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U2 - 10.1038/modpathol.2012.104
DO - 10.1038/modpathol.2012.104
M3 - Article
C2 - 22684219
AN - SCOPUS:84868446982
VL - 25
SP - 1543
EP - 1549
JO - Modern Pathology
JF - Modern Pathology
SN - 0893-3952
IS - 11
ER -