title: Epithelial-to-mesenchymal transition in a fistula-associated anal adenocarcinoma in a patient with long-standing Crohn's disease.
abstract: Anal adenocarcinomas arising from perianal fistulae represent a rare complication in Crohn's disease (CD) patients. We have previously demonstrated the involvement of an epithelial-to-mesenchymal transition (EMT) in the pathogenesis of CD-associated fistulae. Although EMT has also been implicated in the development of colorectal and anal carcinoma, the molecular link from fistula to carcinoma is unclear. We present a case of a 48-year-old White woman who developed a mucinous anal adenocarcinoma originating from a perianal, CD-associated fistula 24 years after being diagnosed with CD. To characterize the expression of EMT-associated molecules in fistula and carcinoma tissue, immunohistochemical analysis for Snail1, Slug, β-catenin and E-cadherin was performed. A mucinous anal adenocarcinoma developed on a perianal fistula in a patient with long-standing CD. After neoadjuvant radiochemotherapy, the fistula-associated tumour was resected and the patient is presently in remission. Using immunohistochemical analysis, we detected a remarkable staining of the Slug transcription factor in transitional cells lining the fistula tract. This observation is unique to this 'carcinoma'-fistula: we had previously shown Slug expression in cells surrounding the fistula tract but not in transitional cells. Expression of Snail1, β-catenin and E-cadherin in this case was comparable with our previous findings. We describe a rare case of a CD fistula-associated adenocarcinoma within an area of squamous epithelium of the perianal area and an unusual expression pattern of EMT markers in this fistula. This case seems to underline the relevance of our previous findings demonstrating that EMT plays an important role for fistula pathogenesis and likely carcinogenesis in CD patients.
authors.affiliation: aDivision of Gastroenterology and Hepatology bInstitute for Surgical Pathology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Michael
authors.initials: M
authors.lastname: Scharl
authors.forename: Pascal
authors.initials: P
authors.lastname: Frei
authors.forename: Sandra M
authors.initials: SM
authors.lastname: Frei
authors.forename: Luc
authors.initials: L
authors.lastname: Biedermann
authors.forename: Achim
authors.initials: A
authors.lastname: Weber
authors.forename: Gerhard
authors.initials: G
authors.lastname: Rogler
mesh_terms: D002288:Adenocarcinoma, Mucinous / Q000737:chemistry / Q000209:etiology* / Q000473:pathology / Q000601:surgery; D015703:Antigens, CD; D001005:Anus Neoplasms / Q000737:chemistry / Q000209:etiology* / Q000473:pathology / Q000601:surgery; D014408:Biomarkers, Tumor / Q000032:analysis; D015820:Cadherins / Q000032:analysis; D059186:Chemoradiotherapy, Adjuvant; D003113:Colonoscopy; D003424:Crohn Disease / Q000150:complications* / Q000175:diagnosis; D019160:Endosonography; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D012003:Rectal Fistula / Q000175:diagnosis / Q000209:etiology*; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000032:analysis; D016896:Treatment Outcome; D051176:beta Catenin / Q000032:analysis
chemical_list: D015703:Antigens, CD; D014408:Biomarkers, Tumor; C513384:CDH1 protein, human; C495270:CTNNB1 protein, human; D015820:Cadherins; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D051176:beta Catenin