title: TMPRSS2-ERG rearrangement in dominant anterior prostatic tumours: incidence and correlation with ERG immunohistochemistry.
abstract: OBJECTIVE
  To study prostate cancer zonal differences in TMPRSS2-ERG gene rearrangement.
  
  
  RESULTS
  We examined 136 well-characterized dominant anterior prostatic tumours, including 61 transition zone (TZ) and 75 anterior peripheral zone (PZ) lesions, defined using strict anatomical considerations. TMPRSS2-ERG FISH and ERG protein immunohistochemistry were performed on tissue microarrays. FISH results, available for 56 TZ and 71 anterior PZ samples, were correlated with ERG staining and TZ-associated 'clear cell' histology. Fewer TZ cancers (four of 56; 7%) were rearranged than anterior PZ cancers (18 of 71; 25%) (P = 0.009); deletion was the sole mechanism of TZ cancer rearrangement. ERG protein overexpression was present in 4% (two of 56; both FISH+) and 30% (21 of 71; 17 FISH+) of TZ and anterior PZ tumours, respectively. 'Clear cell' histology was present in 21 of 56 (38%) TZ and eight of 71 (11%) anterior PZ tumours. Seven per cent of cancers with and 21% without this histology had rearrangement, regardless of zonal origin.
  
  
  CONCLUSIONS
  TMPRSS2-ERG rearrangement occurs in dominant TZ and anterior PZ prostate cancers, with all rearranged TZ cancers in this cohort showing deletion. ERG immunohistochemistry demonstrated excellent sensitivity (86%) and specificity (96%) for TMPRSS2-ERG rearrangement. TMPRSS2-ERG fusion is rare in TZ tumours and present at a low frequency in tumours displaying 'clear cell' histology.
authors.affiliation: Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
authors.forename: Anuradha
authors.initials: A
authors.lastname: Gopalan
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Leversha
authors.forename: Maria E
authors.initials: ME
authors.lastname: Dudas
authors.forename: Alexandra C
authors.initials: AC
authors.lastname: Maschino
authors.forename: Jeremy
authors.initials: J
authors.lastname: Chang
authors.forename: Hikmat A
authors.initials: HA
authors.lastname: Al-Ahmadie
authors.forename: Ying-Bei
authors.initials: YB
authors.lastname: Chen
authors.forename: Satish K
authors.initials: SK
authors.lastname: Tickoo
authors.forename: Victor E
authors.initials: VE
authors.lastname: Reuter
authors.forename: Samson W
authors.initials: SW
authors.lastname: Fine
mesh_terms: D015331:Cohort Studies; D015321:Gene Rearrangement; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D012697:Serine Endopeptidases / Q000235:genetics*; D046888:Tissue Array Analysis; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism*; D000071230:Transcriptional Regulator ERG
chemical_list: C072312:ERG protein, human; D015514:Oncogene Proteins, Fusion; C515553:TMPRSS2-ERG fusion protein, human; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG; D012697:Serine Endopeptidases; C421305:TMPRSS2 protein, human
keywords: TMPRSS2-ERG rearrangement; cancer; immunohistochemistry; prostate; transition zone