Evaluation of the ETS-related gene mRNA in urine for the detection of prostate cancer.
OBJECTIVE
Prevalent gene fusions in prostate cancer involve androgen-regulated promoters (primarily TMPRSS2) and ETS transcription factors (predominantly ETS-regulated gene (ERG)], which result in tumor selective overexpression of ERG in two thirds of patients. Because diverse genomic fusion events lead to ERG overexpression in prostate cancer, we reasoned that it may be more practical to capture such alterations using an assay targeting ERG sequences retained in such gene fusions. This study evaluates the potential of an assay quantitating ERG mRNA in post-digital rectal exam (DRE) urine for improving prostate cancer detection.


METHODS
Patients scheduled to undergo transrectal ultrasound-guided needle biopsy of the prostate were prospectively enrolled. On the day of biopsy, patients provided a urine sample immediately following a DRE. Urine ERG mRNA was measured and normalized to urine prostate-specific antigen (PSA) mRNA using the DTS 400 system. Demographic traits, clinical characteristics and biopsy results were analyzed for association with urine ERG score.


RESULTS
The study was conducted on 237 patients. Prostate cancer was shown on biopsy in 40.9% of study subjects. A higher urine ERG score associated significantly with malignancy on biopsy (P = 0.0145), but not with clinical stage or Gleason score. Urine ERG score performed best in Caucasians and in men with a PSA of <or=4 ng/mL (area under the curve = 0.8).


CONCLUSIONS
A higher urine ERG score in post-DRE urine is associated with the diagnosis of prostate cancer on biopsy. Urine ERG score performed particularly well in men with a PSA of <or=4.0 ng/mL, a segment of the screening population in which further diagnostic markers are needed to determine in whom biopsy should be done.
Urology Service, Walter Reed Army Medical Center, Armed Forces Institute of Pathology, Washington, District of Columbia, USA.
Kevin R
KR
Rice
Yongmei
Y
Chen
Amina
A
Ali
Eric J
EJ
Whitman
Amy
A
Blase
Mona
M
Ibrahim
Sally
S
Elsamanoudi
Stephen
S
Brassell
Bungo
B
Furusato
Norbert
N
Stingle
Isabell A
IA
Sesterhenn
Gyorgy
G
Petrovics
Siobhan
S
Miick
Harry
H
Rittenhouse
Jack
J
Groskopf
David G
DG
McLeod
Shiv
S
Srivastava
D000368:Aged; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics / Q000652:urine; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology / Q000652:urine*; D012333:RNA, Messenger / Q000032:analysis* / Q000235:genetics / Q000652:urine; D012372:ROC Curve; D012680:Sensitivity and Specificity; D015534:Trans-Activators / Q000235:genetics* / Q000652:urine*; D000071230:Transcriptional Regulator ERG
D014408:Biomarkers, Tumor; C072312:ERG protein, human; D012333:RNA, Messenger; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG