title: Quantitative analysis of ERG expression and its splice isoforms in formalin-fixed, paraffin-embedded prostate cancer samples: association with seminal vesicle invasion and biochemical recurrence.
abstract: OBJECTIVE
  The proto-oncogene ETS-related gene (ERG) is consistently overexpressed in prostate cancer. Alternatively spliced isoforms of ERG have variable biological activities; inclusion of exon 11 (72 base pairs [bp]) is associated with aggressiveness and progression of disease. Exon 10 (81 bp) has also been shown to be alternatively spliced. Within this study, we assess whether ERG protein, messenger RNA (mRNA), and ERG splice isoform mRNA expression is altered as prostate cancer progresses.
  
  
  METHODS
  Detection of the TMPRSS2-ERG fusion was done using direct methods (reverse transcription polymerase chain reaction [PCR] and fluorescence in situ hybridization) and indirect methods for ERG mRNA and protein expression using quantitative PCR and immunohistochemistry, respectively. A linear equation method was used to quantitatively determine relative proportions of ERG variants (ERG72/Δ72, ERG81/Δ81) for each sample.
  
  
  RESULTS
  ERG mRNA and protein expression is increased in patients with advanced prostate cancer, with higher levels of ERG expression significantly associated with seminal vesicle invasion (stage pT3b) and biochemical recurrence. Genes involved in cell migration and invasiveness (matrix metalloproteinase 7, osteopontin, and septin 9) are increased in prostate cancers that overexpress ERG. In addition, there is a clear indication of increased retention of exons 10 and 11 in prostate cancer.
  
  
  CONCLUSIONS
  Analysis of ERG and its variants may be valuable in determining prognosis and development of prostate cancer.
authors.affiliation: From the Faculty of Health & Life Sciences, University of the West of England, Bristol, UK;
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Hagen
authors.affiliation: From the Faculty of Health & Life Sciences, University of the West of England, Bristol, UK;
authors.forename: Patricia
authors.initials: P
authors.lastname: Adamo
authors.affiliation: Department of Cellular Histopathology, North Bristol NHS Trust, Bristol, UK;
authors.forename: Saima
authors.initials: S
authors.lastname: Karamat
authors.affiliation: Department of Cellular Histopathology, North Bristol NHS Trust, Bristol, UK;
authors.forename: Jon
authors.initials: J
authors.lastname: Oxley
authors.affiliation: North Bristol NHS Trust, Bristol, UK; and.
authors.forename: Jonathan J
authors.initials: JJ
authors.lastname: Aning
authors.affiliation: North Bristol NHS Trust, Bristol, UK; and.
authors.forename: David
authors.initials: D
authors.lastname: Gillatt
authors.affiliation: North Bristol NHS Trust, Bristol, UK; and.
authors.forename: Raj
authors.initials: R
authors.lastname: Persad
authors.affiliation: From the Faculty of Health & Life Sciences, University of the West of England, Bristol, UK;
authors.forename: Michael R
authors.initials: MR
authors.lastname: Ladomery
authors.affiliation: From the Faculty of Health & Life Sciences, University of the West of England, Bristol, UK; Department of Pathology, University of Malaya Medical Centre, Kuala Lumpur, Malaysia. Anthony.Rhodes@ummc.edu.my.
authors.forename: Anthony
authors.initials: A
authors.lastname: Rhodes
mesh_terms: D017398:Alternative Splicing; D005091:Exons / Q000235:genetics; D005557:Formaldehyde; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D009361:Neoplasm Invasiveness; D015514:Oncogene Proteins, Fusion / Q000235:genetics* / Q000378:metabolism; D016612:Paraffin Embedding; D011467:Prostate / Q000473:pathology; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D020033:Protein Isoforms; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D012669:Seminal Vesicles / Q000473:pathology; D012697:Serine Endopeptidases / Q000235:genetics* / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D000071230:Transcriptional Regulator ERG
chemical_list: C072312:ERG protein, human; C000715470:MAS1 protein, human; D015514:Oncogene Proteins, Fusion; D020033:Protein Isoforms; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG; D005557:Formaldehyde; D012697:Serine Endopeptidases; C421305:TMPRSS2 protein, human
keywords: ERG isoforms; FFPE; Prostate cancer; TMPRSS2-ERG