title: Combined analysis of TMPRSS2-ERG and TERT for improved prognosis of biochemical recurrence in prostate cancer.
abstract: Prostate cancer (PCa) is a heterogeneous disease with diverse clinical outcomes. TMPRSS2-ERG is the most common gene fusion in PCa, whereas activation of telomerase is a common feature of various malignancies. The aim of our study was to explore the combined utility of these and some other biomarkers in predicting biochemical recurrence after radical prostatectomy. Prostate specimens and urine sediments from 179 previously untreated patients with pT2-pT3 stage PCa were analyzed for expression of telomerase (TERT and TR) and the TMPRSS2-ERG fusion gene by means of reverse transcription PCR. Real-time PCR was used for quantification of ERG and SPINK1 expression. In total, 74% (117/158) of the prostate adenocarcinomas were positive for the TMPRSS2-ERG and/or TERT expression. Noninvasively, these transcripts were identified in 31% (19/61) of catheterized urine specimens. Significantly higher expression of ERG was detected in TMPRSS2-ERG-positive tumors (P<0.0001), whereas more intense expression of SPINK1 was characteristic for the TMPRSS2-ERG-negative tumors (P=0.003). TERT-positive cases also had elevated levels of ERG (P=0.016), suggesting a possible link between aberrant expression of ERG and reactivation of TERT in prostate tumors. The cases negative for both transcripts, TMPRSS2-ERG and TERT, rarely recurred (P=0.014) and showed significantly longer biochemical recurrence-free period (P=0.022) as compared to the TMPRSS2-ERG and/or TERT-positive cases. The results of our study suggest that combined analysis of TMPRSS2-ERG and TERT expression can be a valuable tool for early prediction of biochemical recurrence of PCa after radical prostatectomy.
authors.affiliation: Division of Human Genome Research Centre, Faculty of Natural Sciences, Vilnius University, and National Center of Pathology, Urology Department, Vilnius University Hospital Santariskiu Clinics, Vilnius, Lithuania.
authors.forename: Rasa
authors.initials: R
authors.lastname: Sabaliauskaite
authors.forename: Sonata
authors.initials: S
authors.lastname: Jarmalaite
authors.forename: Donatas
authors.initials: D
authors.lastname: Petroska
authors.forename: Darius
authors.initials: D
authors.lastname: Dasevicius
authors.forename: Arvydas
authors.initials: A
authors.lastname: Laurinavicius
authors.forename: Feliksas
authors.initials: F
authors.lastname: Jankevicius
authors.forename: Juozas R
authors.initials: JR
authors.lastname: Lazutka
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics / Q000378:metabolism / Q000652:urine; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D015514:Oncogene Proteins, Fusion / Q000032:analysis* / Q000235:genetics / Q000378:metabolism / Q000652:urine; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000737:chemistry / Q000175:diagnosis* / Q000378:metabolism* / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018709:Statistics, Nonparametric; D019098:Telomerase / Q000032:analysis* / Q000235:genetics / Q000378:metabolism / Q000652:urine; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D000071230:Transcriptional Regulator ERG; D014359:Trypsin Inhibitor, Kazal Pancreatic
chemical_list: D014408:Biomarkers, Tumor; D002352:Carrier Proteins; C072312:ERG protein, human; D015514:Oncogene Proteins, Fusion; C486642:SPINK1 protein, human; C515553:TMPRSS2-ERG fusion protein, human; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG; D014359:Trypsin Inhibitor, Kazal Pancreatic; C509186:TERT protein, human; D019098:Telomerase