Performance of a Single Assay for Both Type III and Type VI TMPRSS2:ERG Fusions in Noninvasive Prediction of Prostate Biopsy Outcome

Clark, Jarrod; Munson, K. W.; Gu, Jessie; Lamparska-Kupsik, Katarzyna; Chan, Kevin; Yoshida, Jeffrey; Kawachi, Mark H.; Crocitto, Laura E.; Wilson, Timothy G.; Feng, Ziding; Smith, Steven S.

doi:10.1373/clinchem.2008.108845

Cited by 25 publications

(21 citation statements)

References 19 publications

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“…Two other studies investigated TMPRSS2:ERG fusion in urine and reported similarly high specificities of 93% and 73%, respectively; and one study evaluated TMPRSS2:ERG fusion in expressed prostatic secretions reporting a specificity of 80%. 23 However, prior studies have not evaluated the utility of combining serum PSA test results with noninvasive detection of TMPRSS2:ERG and PCA3 in developing models to predict prostate cancer diagnosis in a clinically relevant context, as we explored in this study.…”

Section: Commentmentioning

confidence: 99%

Combining urinary detection of TMPRSS2:ERG and PCA3 with serum PSA to predict diagnosis of prostate cancer

Salami

Schmidt

Laxman

et al. 2013

Urologic Oncology: Seminars and Original Investigations

186

120

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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 two centers; 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 to 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 ≥10ng/ml, while restricting biopsy among those with PSA <10ng/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.

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Section: Commentmentioning

confidence: 99%

Combining urinary detection of TMPRSS2:ERG and PCA3 with serum PSA to predict diagnosis of prostate cancer

Salami

Schmidt

Laxman

et al. 2013

Urologic Oncology: Seminars and Original Investigations

186

120

View full text Add to dashboard Cite

show abstract

“…Because a diagnostic strategy based on prostate tissue is inadequate for clinical application, noninvasive methods, similar to those for PCA3 (18 ), were developed to detect the fusion transcripts in urine (19 -23 ) voided after digital rectal examination (DRE). In contrast with a very high diagnostic specificity (Ͼ90%) and a very good predictive value for positive biopsy, the overall diagnostic sensitivity of the test was reported to be only around 50%, although it could be improved by combining results with PSA, DRE (21 ), and PCA3 (20,23 ). One drawback of those studies was the inability to match findings in urine with those in prostate tissue in the same patient.…”

mentioning

confidence: 99%

TMPRSS2-ERG Fusion Transcripts in Matched Urine and Needle Rinse Material after Biopsy for the Detection of Prostate Cancer

Bories

Younès²,

Zerbib

et al. 2013

Clinical Chemistry

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“…Several studies have indicated that TMPRSS2 -ERG fusions confer a worse prognosis (Nam et al, 2007;Attard et al, 2008a;Clark et al, 2008), whereas others have not . Discrepancies in the reported prognostic significance of TMPRSS2 -ERG fusions can be explained in a similar manner by factors affecting the variation in prevalence of TMPRSS2 -ERG (i.e., cohort race/ethnicity, fusion detection technique), and are also liable to the primary end point of the study (i.e., biochemical recurrence, overall survival).…”

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confidence: 99%

Prostate cancer genes associated with TMPRSS2–ERG gene fusion and prognostic of biochemical recurrence in multiple cohorts

et al. 2010

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BACKGROUND: Recent studies have indicated that prostate cancer patients with the TMPRSS2 -ERG gene fusion have a higher risk of recurrence. To identify markers associated with TMPRSS2 -ERG fusion and prognostic of biochemical recurrence, we analysed a cohort of 139 men with prostate cancer for 502 molecular markers. METHODS: RNA from radical prostatectomy tumour specimens was analysed using cDNA-mediated, annealing, selection, extension and ligation (DASL) to determine mRNAs associated with TMPRSS2 -ERG T1/E4 fusion and prognostic of biochemical recurrence. Differentially expressed mRNAs in T1/E4-positive tumours were determined using significance analysis of microarrays (false discovery rate (FDR) o5%). Univariate and multivariate Cox regression determined genes, gene signatures and clinical factors prognostic of recurrence (P-value o0.05, log -rank test). Analysis of two prostate microarray studies (GSE1065 and GSE8402) validated the findings. RESULTS: In the 139 patients from this study and from a 455-patient Swedish cohort, 15 genes in common were differentially regulated in T1/E4 fusion-positive tumours (FDR o0.05). The most significant mRNAs in both cohorts coded ERG. Nine genes were found prognostic of recurrence in this study and in a 596-patient Minnesota cohort. A molecular recurrence score was significant in prognosticating recurrence (P-value 0.000167) and remained significant in multivariate analysis of a mixed clinical model considering Gleason score and TMPRSS2 -ERG fusion status. CONCLUSIONS: TMPRSS2 -ERG T1/E4 fusion-positive tumours had differentially regulated mRNAs observed in multiple studies, the most significant one coded for ERG. Several mRNAs were consistently associated with biochemical recurrence and have potential clinical utility but will require further validation for successful translation.

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Performance of a Single Assay for Both Type III and Type VI TMPRSS2:ERG Fusions in Noninvasive Prediction of Prostate Biopsy Outcome

Cited by 25 publications

References 19 publications

Combining urinary detection of TMPRSS2:ERG and PCA3 with serum PSA to predict diagnosis of prostate cancer

Combining urinary detection of TMPRSS2:ERG and PCA3 with serum PSA to predict diagnosis of prostate cancer

TMPRSS2-ERG Fusion Transcripts in Matched Urine and Needle Rinse Material after Biopsy for the Detection of Prostate Cancer

Prostate cancer genes associated with TMPRSS2–ERG gene fusion and prognostic of biochemical recurrence in multiple cohorts

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