title: Transcription factor E2F3 overexpressed in prostate cancer independently predicts clinical outcome.
abstract: E2F transcription factors, including E2F3, directly modulate expression of EZH2. Recently, overexpression of the EZH2 gene has been implicated in the development of human prostate cancer. In tissue microrarray studies we now show that expression of high levels of nuclear E2F3 occurs in a high proportion (98/147, 67%) of human prostate cancers, but is a rare event in non-neoplastic prostatic epithelium suggesting a role for E2F3 overexpression in prostate carcinogenesis. Patients with prostate cancer exhibiting immunohistochemically detectable nuclear E2F3 expression have poorer overall survival (P=0.0022) and cause-specific survival (P=0.0047) than patients without detectable E2F3 expression. When patients are stratified according to the maximum percentage of E2F3-positive nuclei identified within their prostate cancers (up to 20, 21-40%, etc.), there is an increasingly significant association between E2F3 staining and risk of death both for overall survival (P=0.0014) and for cause-specific survival (P=0.0004). Multivariate analyses select E2F3 expression as an independent factor predicting overall survival (unstratified P=0.0103, stratified P=0.0086) and cause-specific survival (unstratified P=0.0288, stratified P=0.0072). When these results are considered together with published data on EZH2 and on the E2F3 control protein pRB, we conclude that the pRB-E2F3-EZH2 control axis may have a critical role in modulating aggressiveness of individual human prostate cancer.
authors.affiliation: Department of Pathology and Molecular Genetics, University of Liverpool, Duncan Building, Liverpool, UK.
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Foster
authors.forename: Alison
authors.initials: A
authors.lastname: Falconer
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Dodson
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Norman
authors.forename: Nening
authors.initials: N
authors.lastname: Dennis
authors.forename: Anne
authors.initials: A
authors.lastname: Fletcher
authors.forename: Christine
authors.initials: C
authors.lastname: Southgate
authors.forename: Anna
authors.initials: A
authors.lastname: Dowe
authors.forename: David
authors.initials: D
authors.lastname: Dearnaley
authors.forename: Sameer
authors.initials: S
authors.lastname: Jhavar
authors.forename: Rosalind
authors.initials: R
authors.lastname: Eeles
authors.forename: Andrew
authors.initials: A
authors.lastname: Feber
authors.forename: Colin S
authors.initials: CS
authors.lastname: Cooper
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D050699:E2F3 Transcription Factor; D005784:Gene Amplification; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000737:chemistry / Q000401:mortality* / Q000473:pathology; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics / Q000502:physiology*
chemical_list: D050699:E2F3 Transcription Factor; C098319:E2F3 protein, human; D014157:Transcription Factors