Loss of PTEN expression is associated with increased risk of recurrence after prostatectomy for clinically localized prostate cancer.
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 case-control 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%, P=0.05) and PTEN loss (40 vs 31%, P=0.02) than controls. Men with markedly decreased PTEN staining had a higher risk of recurrence (odds ratio=1.67; 95% confidence intervals 1.09, 2.57; P=0.02) 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.
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
Alcides
A
Chaux
Sarah B
SB
Peskoe
Nilda
N
Gonzalez-Roibon
Luciana
L
Schultz
Roula
R
Albadine
Jessica
J
Hicks
Angelo M
AM
De Marzo
Elizabeth A
EA
Platz
George J
GJ
Netto
D014408:Biomarkers, Tumor / Q000032:analysis* / Q000097:blood; D002277:Carcinoma / Q000097:blood / Q000201:enzymology* / Q000556:secondary / Q000601:surgery*; D016022:Case-Control Studies; D015536:Down-Regulation; D006801:Humans; D007150:Immunohistochemistry; D007610:Kallikreins / Q000097:blood; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local; D016017:Odds Ratio; D051059:PTEN Phosphohydrolase / Q000032:analysis*; D017430:Prostate-Specific Antigen / Q000097:blood; D011468:Prostatectomy / Q000009:adverse effects; D011471:Prostatic Neoplasms / Q000097:blood / Q000201:enzymology* / Q000473:pathology / Q000601:surgery*; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
D014408:Biomarkers, Tumor; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; C549870:KLK3 protein, human; D007610:Kallikreins; D017430:Prostate-Specific Antigen