Prostate cancer molecular markers GSTP1 and hTERT in expressed prostatic secretions as predictors of biopsy results.
OBJECTIVE
To develop noninvasive diagnostic tools for the early detection of prostate cancer (PCa). Current screening for PCa lacks sensitivity and specificity. Two molecular markers, telomerase activity and aberrant methylation of the glutathione S-transferase P1 (GSTP1) promoter, are found in more than 90% of PCa specimens. Additionally, these markers can be detected in bodily fluids such as urine and postprostatic massage urethral washes.


METHODS
Expressed prostatic secretions (EPS) from men being evaluated for PCa were analyzed for human telomerase reverse transcriptase (hTERT) expression (the critical factor for telomerase activity) and GSTP1 methylation status. The results were compared with the prostate needle biopsy findings.


RESULTS
EPS could be obtained from 86% of all subjects, and 90% of these samples yielded sufficient RNA and/or DNA for assaying. hTERT expression from EPS (n = 49) had 36% sensitivity and 66% specificity, and GSTP1 methylation from EPS (n = 58) had 46% sensitivity and 56% specificity for the detection of PCa. The combined analysis (n = 32) of hTERT and GSTP1 had 73% sensitivity and 43% specificity, giving a positive predictive value of 40% and a negative predictive value of 75%.


CONCLUSIONS
These results demonstrate that EPS can be successfully obtained and easily tested for hTERT expression and GSTP1 methylation. Tests with a high negative predictive value, such as our combination assay results, could be useful in augmenting current PCa diagnostic procedures. For example, the examination of EPS for hTERT and GSTP1 methylation in patients with an elevated prostate-specific antigen level might be used in predicting which patients will have negative biopsies. The use of this assay could potentially eliminate up to 30% of costly and invasive needle biopsies.
Crocitto
Laura E
LE
City of Hope National Medical Center, Duarte, California 91010, USA.
Korns
Darlynn
D
Kretzner
Leo
L
Shevchuk
Taras
T
Blair
Sarah L
SL
Wilson
Timothy G
TG
Ramin
Soroush A
SA
Kawachi
Mark H
MH
Smith
Steven S
SS
D000230:Adenocarcinoma / Q000737:chemistry* / Q000175:diagnosis / Q000473:pathology; D014408:Biomarkers, Tumor / Q000032:analysis*; D001707:Biopsy, Needle; D001826:Body Fluids / Q000737:chemistry*; D004268:DNA-Binding Proteins; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase / Q000032:analysis*; D006801:Humans; D007527:Isoenzymes / Q000032:analysis*; D008297:Male; D008745:Methylation; D009363:Neoplasm Proteins / Q000032:analysis*; D011237:Predictive Value of Tests; D011471:Prostatic Neoplasms / Q000737:chemistry* / Q000175:diagnosis / Q000473:pathology; D011499:Protein Processing, Post-Translational; D012680:Sensitivity and Specificity; D019098:Telomerase / Q000032:analysis*
D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D007527:Isoenzymes; D009363:Neoplasm Proteins; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; D019098:Telomerase