title: Expression of the androgen-regulated fusion gene TMPRSS2-ERG does not predict response to endocrine treatment in hormone-naïve, node-positive prostate cancer.
abstract: BACKGROUND
  Fusion of the androgen-regulated gene transmembrane protease, serine 2, TMPRSS2, to the v-ets erythroblastosis virus E26 oncogene homolog (avian), ERG, of the erythroblast transformation-specific (ETS) family is the most common genetic alteration in prostate cancer (PCa).
  
  
  OBJECTIVE
  To determine whether expression of androgen-regulated TMPRSS2-ERG predicts response to endocrine treatment in hormone-naïve, node-positive PCa.
  
  
  METHODS
  Eighty-five patients with histologically confirmed, node-positive PCa who were without treatment at the moment of lymph node dissection were analysed. RNA was isolated from the paraffin-embedded lymph node metastases and complementary DNA (cDNA) was made. The quality of cDNA was tested by polymerase chain reaction (PCR) analysis of the expression of the housekeeping gene hydroxymethylbilane synthase, HMBS (formerly PBGD). TMPRSS2-ERG expression was analysed by PCR using a forward primer in TMPRSS2 exon 1 and a reverse primer in ERG exon 4.
  
  
  METHODS
  The primary end point was time from start of endocrine therapy to the occurrence of three consecutive rises in prostate-specific antigen (PSA) that were at least 2 wk apart and resulted in two 50% increases over the PSA nadir. Secondary end points were time to PSA nadir after start of endocrine treatment and cancer-specific and overall survival.
  
  
  CONCLUSIONS
  TMPRSS2-ERG was expressed in 59% of the 71 patients who could be analysed. Median duration of response to endocrine therapy was 20.9 mo versus 24.1 mo for gene fusion-positive versus gene fusion-negative patients (95% confidence intervals: 18.6-23.1 vs 18.9-29.4, p=0.70). Furthermore, no significant differences were seen between the two groups for the secondary end points.
  
  
  CONCLUSIONS
  Expression of TMPRSS2-ERG is frequent in lymph node metastases of patients with untreated PCa; however, expression of this androgen-regulated fusion gene did not correspond with duration of response to endocrine therapy. Our results suggest that expression of TMPRSS2-ERG is not a candidate marker to select for metastatic PCa patients who will benefit more from endocrine treatment.
authors.affiliation: Department of Urology, Erasmus Medical Centre Rotterdam, Rotterdam, The Netherlands.
authors.forename: Joost L
authors.initials: JL
authors.lastname: Boormans
authors.forename: Karin G
authors.initials: KG
authors.lastname: Hermans
authors.forename: Angelique C J Ziel-van der
authors.initials: AC
authors.lastname: Made
authors.forename: Geert J H L
authors.initials: GJ
authors.lastname: van Leenders
authors.forename: Mark F
authors.initials: MF
authors.lastname: Wildhagen
authors.forename: Laurence
authors.initials: L
authors.lastname: Collette
authors.forename: Fritz H
authors.initials: FH
authors.lastname: Schröder
authors.forename: Jan
authors.initials: J
authors.lastname: Trapman
authors.forename: Paul C M S
authors.initials: PC
authors.lastname: Verhagen
mesh_terms: D000726:Androgen Antagonists / Q000627:therapeutic use; D015972:Gene Expression Regulation, Neoplastic; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D015514:Oncogene Proteins, Fusion / Q000096:biosynthesis* / Q000235:genetics; D009919:Orchiectomy; D011237:Predictive Value of Tests; D011471:Prostatic Neoplasms / Q000235:genetics / Q000473:pathology* / Q000628:therapy*
chemical_list: D000726:Androgen Antagonists; D015514:Oncogene Proteins, Fusion; C515553:TMPRSS2-ERG fusion protein, human; D007987:Gonadotropin-Releasing Hormone