Title | Combining urinary detection of TMPRSS2:ERG and PCA3 with serum PSA to predict diagnosis of prostate cancer. |
Publication Type | Journal Article |
Year of Publication | 2013 |
Authors | Salami SS, Schmidt F, Laxman B, Regan MM, Rickman DS, Scherr D, Bueti G, Siddiqui J, Tomlins SA, Wei JT, Chinnaiyan AM, Rubin MA, Sanda MG |
Journal | Urol Oncol |
Volume | 31 |
Issue | 5 |
Pagination | 566-71 |
Date Published | 2013 Jul |
ISSN | 1873-2496 |
Keywords | Aged, Antigens, Neoplasm, Biomarkers, Tumor, Biopsy, Humans, Logistic Models, Male, Middle Aged, Multivariate Analysis, Oncogene Proteins, Fusion, Predictive Value of Tests, Prostate, Prostate-Specific Antigen, Prostatic Neoplasms, Reverse Transcriptase Polymerase Chain Reaction |
Abstract | OBJECTIVES: We sought to develop a clinical algorithm combining serum PSA with detection of TMPRSS2:ERG fusion and PCA3 in urine collected after digital rectal exam (post-DRE urine) to predict prostate cancer on subsequent biopsy. MATERIALS AND METHODS: Post-DRE urine was collected in 48 consecutive patients before prostate biopsy at 2 centers; quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to detect PCA3 and TMPRSS2:ERG fusion transcript expression. Serum PSA was measured by clinical assay. The performance of TMPRSS2:ERG fusion, PCA3, and serum PSA as biomarkers predicting prostate cancer at biopsy was measured; a clinically practical algorithm combining serum PSA with TMPRSS2:ERG and PCA3 in post-DRE urine to predict prostate cancer was developed. RESULTS: Post-DRE urine sediment provided informative RNA in 45 patients; prostate cancer was present on subsequent biopsy in 15. TMPRSS2:ERG in post-DRE urine was associated with prostate cancer (OR = 12.02; P < 0.001). PCA3 had the highest sensitivity in predicting prostate cancer diagnosis (93%), whereas TMPRSS2:ERG had the highest specificity (87%). TMPRSS2:ERG had the greatest discriminatory value in predicting prostate cancer (AUC = 0.77 compared with 0.65 for PCA3 and 0.72 for serum PSA alone). Combining serum PSA, PCA3, and TMPRSS2:ERG in a multivariable algorithm optimized for clinical utility improved cancer prediction (AUC = 0.88; specificity = 90% at 80% sensitivity). CONCLUSIONS: A clinical algorithm specifying biopsy for all patients with PSA ≥ 10 ng/ml, while restricting biopsy among those with PSA <10 ng/ml to only those with detectable PCA3 or TMPRSS2:ERG in post-DRE urine, performed better than the individual biomarkers alone in predicting prostate cancer. |
DOI | 10.1016/j.urolonc.2011.04.001 |
Alternate Journal | Urol Oncol |
PubMed ID | 21600800 |
PubMed Central ID | PMC3210917 |
Grant List | R01 CA179100 / CA / NCI NIH HHS / United States U01 CA113913 / CA / NCI NIH HHS / United States U01 CA113913-05S1 / CA / NCI NIH HHS / United States U01 CA113913-06 / CA / NCI NIH HHS / United States U01 CA113913-07 / CA / NCI NIH HHS / United States |
Related Lab:
Related Faculty:
David Rickman, Ph.D.