A duplex quantitative polymerase chain reaction assay based on quantification of alpha-methylacyl-CoA racemase transcripts and prostate cancer antigen 3 in urine sediments improved diagnostic accuracy for prostate cancer.
OBJECTIVE
Most men with increased serum prostate specific antigen and negative biopsy require repeat biopsy because of the lack of a sensitive and specific prostate cancer detection test. In this study we evaluated the diagnostic potential of a duplex assay for prostate cancer by quantifying transcript levels of alpha-methylacyl-CoA racemase and prostate cancer antigen 3 in urine sediments following prostatic massage.


METHODS
Urine sediments from 92 patients, 43 with and 49 without prostate cancer, were collected after digital rectal examination. Transcript levels of AMACR, PCA3 and PSA in total RNA isolated from these samples were determined by absolute quantitative real-time polymerase chain reaction. AMACR and PCA3 scores were obtained by normalizing the transcript level to that of prostate specific antigen for each sample and multiplying by 100.


RESULTS
AMACR (p = 0.006) and PCA3 (p = 0.014) scores, but not serum prostate specific antigen (p = 0.306), distinguished specimens from patients with prostate cancer from specimens from patients without prostate cancer, and ROC analysis established the diagnostic cutoff scores for the AMACR and PCA3 tests at 10.7 and 19.9, respectively. As determined from these cutoff scores the AMACR test had 70% (95% CI 56-83) sensitivity and 71% (95% CI 59-84) specificity, whereas the PCA3 test had 72% (95% CI 59-85) sensitivity and 59% (95% CI 45-73) specificity for prostate cancer detection. The combined use of AMACR and PCA3 scores in a dual marker test increased sensitivity to 81% (95% CI 70-93) and specificity to 84% (95% CI 73-94).


CONCLUSIONS
Urinary AMACR and PCA3 tests were superior to a serum prostate specific antigen test for detecting prostate cancer. Their combined use in a dual marker test further improved sensitivity and accuracy, and could serve as a surveillance test after repeat negative prostate biopsies.
Department of Environmental Health, University of Cincinnati Medical Center, Cincinnati, Ohio 45267, USA.
Bin
B
Ouyang
Bruce
B
Bracken
Barbara
B
Burke
Ethan
E
Chung
Juan
J
Liang
Shuk-Mei
SM
Ho
D000368:Aged; D000951:Antigens, Neoplasm / Q000652:urine*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction / Q000379:methods*; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000652:urine*; D019998:Racemases and Epimerases / Q000235:genetics / Q000652:urine*; D015203:Reproducibility of Results; D014158:Transcription, Genetic
D000951:Antigens, Neoplasm; C479341:prostate cancer antigen 3, human; D019998:Racemases and Epimerases; C108352:alpha-methylacyl-CoA racemase