TMPRSS2:ERG fusion transcripts in urine from prostate cancer patients correlate with a less favorable prognosis.
The transcription factor ERG is highly upregulated in the majority of prostate cancers due to chromosomal fusion of the androgen responsive promoter of TMPRSS2 to the ERG reading frame. Our aim was to identify this gene fusion in urine samples from prostate cancer patients prior to radical treatment and to compare fusion status with clinicopathological variables. Urine fractions from 55 patients (with and without prior prostatic massage) were analyzed for the presence of TMPRSS2:ERG isoforms using real-time qPCR. Sixty-nine percent of urine samples following prostatic massage were positive for TMPRSS2:ERG isoforms a or b, five out of which were positive for both, vs 24% of samples obtained without prior massage. Isoform a seems to be most prevalent and some patients may be positive for more than one fusion variant, reflecting the multifocality of prostate cancer. Prostatic massage prior to sampling, analysis of pelleted urine material and detection of cDNA provided the highest sensitivity. Positive statistical correlations were identified between TMPRSS2:ERG fusion and high s-PSA, pathological stage and Gleason score. Our findings contribute to the increasing elucidation of the role of TMPRSS2:ERG in the development of prostate cancer.
Rostad
Kari
K
The Gade Institute, University of Bergen, Bergen, Norway.
Hellwinkel
Olaf J C
OJ
Haukaas
Svein A
SA
Halvorsen
Ole J
OJ
Øyan
Anne M
AM
Haese
Alexander
A
Budäus
Lars
L
Albrecht
Heiko
H
Akslen
Lars A
LA
Schlomm
Thorsten
T
Kalland
Karl-Henning
KH
D000368:Aged; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000235:genetics / Q000652:urine*; D045744:Cell Line, Tumor; D005091:Exons; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D011379:Prognosis; D017430:Prostate-Specific Antigen / Q000652:urine; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000652:urine*; D020033:Protein Isoforms / Q000235:genetics; D012334:RNA, Neoplasm / Q000652:urine*; D012680:Sensitivity and Specificity; D014158:Transcription, Genetic
D014408:Biomarkers, Tumor; D015514:Oncogene Proteins, Fusion; D020033:Protein Isoforms; D012334:RNA, Neoplasm; C515553:TMPRSS2-ERG fusion protein, human; D017430:Prostate-Specific Antigen