Putative prognostic epithelial-to-mesenchymal transition biomarkers for aggressive prostate cancer.
Prostate cancer is the second most frequently diagnosed cancer worldwide and is the sixth leading cause of cancer deaths in men, yet it varies greatly in its aggressiveness. Currently, it is not possible to adequately differentiate between patients whose tumors will remain indolent and those patients whose disease will progress, resulting in unnecessary aggressive treatment. Consequently, there is an urgent need to identify markers of prostate cancer progression, invasiveness and metastasis to more accurately predict prognosis. The aim of this study was to assess the ability of key epithelial-to-mesenchymal transition molecules in identifying prostate cancer patients who are likely to develop aggressive tumors. Using 215 archival patient tissue samples, immunohistochemistry was applied to examine the expression and sub-cellular localization of E-Cadherin, Snail, Slug, Twist, Vimentin, BMP-2 and BMP-7. Of the seven markers assessed, a significantly increased expression of Snail protein was observed within the nucleus of prostate cancer cells and was strongly associated with increasing Gleason score and clinical stage. In addition, loss of E-Cadherin expression at the cellular membrane of prostate cancer cells was also significantly associated with increasing Gleason score, clinical stage, and additionally, a reduction in survival.
College of Medicine, Swansea University, Swansea SA2 8PP, Wales, UK.
Helen
H
Whiteland
Samantha
S
Spencer-Harty
David Hywel
DH
Thomas
Christine
C
Davies
Claire
C
Morgan
Howard
H
Kynaston
Pradeep
P
Bose
Neil
N
Fenn
Paul D
PD
Lewis
Owen
O
Bodger
Spencer
S
Jenkins
Shareen H
SH
Doak
D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D015820:Cadherins / Q000032:analysis / Q000096:biosynthesis; D058750:Epithelial-Mesenchymal Transition; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000032:analysis / Q000096:biosynthesis
D014408:Biomarkers, Tumor; D015820:Cadherins; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors
Clinical stage; E-Cadherin; Epithelial-to-mesenchyme transition; Gleason score; Prostate cancer; Snail