Transcription factor E2F3 overexpressed in prostate cancer independently predicts clinical outcome

• Published in: Oncogene Vol. 23; no. 35; pp. 5871 - 5879
• Main Authors: FOSTER, Christopher S, FALCONER, Alison, EELES, Rosalind, FEBER, Andrew, COOPER, Colin S, DODSON, Andrew R, NORMAN, Andrew R, DENNIS, Nening, FLETCHER, Anne, SOUTHGATE, Christine, DOWE, Anna, DEARNALEY, David, JHAVAR, Sameer
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing 05-08-2004; Nature Publishing Group
• Subjects: Adult; Aged; Aged, 80 and over; Biological and medical sciences; Carcinogenesis; Cell physiology; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Clinical outcomes; E2F protein; E2F3 Transcription Factor; Epithelium; EZH2 gene; Fundamental and applied biological sciences. Psychology; Gene Amplification; Gynecology. Andrology. Obstetrics; Humans; Immunohistochemistry; Male; Male genital diseases; Medical sciences; Middle Aged; Molecular and cellular biology; Nephrology. Urinary tract diseases; Patients; Prostate cancer; Prostatic Neoplasms - chemistry; Prostatic Neoplasms - mortality; Prostatic Neoplasms - pathology; Survival; Transcription factors; Transcription Factors - analysis; Transcription Factors - genetics; Transcription Factors - physiology; Tumors; Tumors of the urinary system; Urinary tract. Prostate gland; E2F3 gene; Prostate disease; Transcription factor E2F; EZH2 gene; Tumor; Male genital diseases; Carcinogenesis; Prostate; Prostate cancer
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/sj.onc.1207800

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.