title: Morphological and immunohistochemical identification of epithelial-to-mesenchymal transition in clinical prostate cancer.
abstract: Epithelial-to-mesenchymal transition (EMT) is a process known to be associated with aggressive tumor behavior, metastasis and treatment resistance. It is characterized by coincidental upregulation of mesenchymal markers such as vimentin, fibronectin and N-cadherin concurrent with E-cadherin downregulation. Studies on EMT are generally performed in cell lines and mouse models, while the histopathological and phenotypical properties in clinical prostate cancer (PCa) are still unclear. The objective of this study was to identify EMT in PCa patients. We demonstrated that N-cadherin, vimentin and fibronectin were generally not co-expressed in corresponding tumor regions. Immunofluorescent double stainings confirmed that co-expression of mesenchymal markers was uncommon, as we found no prostate cancer cells that co-expressed N-cadherin with fibronectin and only rare (<1%) cells that co-expressed N-cadherin with vimentin. Downregulation of E-cadherin was demonstrated in all N-cadherin positive tumor cells, but not in vimentin or fibronectin positive tumor cells. We further analyzed N-cadherin expression in morphologically distinct PCa growth patterns in a radical prostatectomy cohort (n = 77) and found that N-cadherin is preferentially expressed in ill-defined Gleason grade 4 PCa. In conclusion, we demonstrate that N-cadherin is the most reliable marker for EMT in clinical PCa and is preferentially expressed in ill-defined Gleason grade 4 growth pattern.
authors.affiliation: Department of Pathology, Erasmus Medical Centre, Rotterdam, The Netherlands.
authors.forename: Kimberley
authors.initials: K
authors.lastname: Kolijn
authors.affiliation: Department of Pathology, Erasmus Medical Centre, Rotterdam, The Netherlands.
authors.forename: Esther I
authors.initials: EI
authors.lastname: Verhoef
authors.affiliation: Department of Pathology, Erasmus Medical Centre, Rotterdam, The Netherlands.
authors.forename: Geert J L H
authors.initials: GJ
authors.lastname: van Leenders
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D015820:Cadherins / Q000096:biosynthesis*; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D005353:Fibronectins / Q000096:biosynthesis*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000473:pathology*; D015398:Signal Transduction; D014746:Vimentin / Q000096:biosynthesis*
chemical_list: D014408:Biomarkers, Tumor; D015820:Cadherins; D005353:Fibronectins; D014746:Vimentin
keywords: N-cadherin; epithelial-to-mesenchymal transition; ill-defined; prostate cancer