title: Small bowel adenocarcinomas complicating Crohn's disease are associated with dysplasia: a pathological and molecular study.
abstract: BACKGROUND
  Crohn's disease (CD) is associated with an increased risk of small bowel adenocarcinoma (SBA). However, there are no guidelines for the screening and early diagnosis of SBA. Colorectal cancer associated with chronic colitis arises from dysplasia. High-risk patients benefit from surveillance colonoscopies aimed to detect dysplasia. The dysplasia-carcinoma sequence remains poorly documented in CD-associated SBA. Moreover, molecular data about SBA complicating CD and associated dysplasia are very limited. We therefore assessed dysplasia and several key molecular markers of carcinogenesis in SBA and dysplasia developed in patients with CD.
  
  
  METHODS
  Forty-five SBA complicating CD and 4 specimens with dysplasia without SBA were screened. In SBA, we looked for dysplasia and determined their pathological characteristics (type, grade, distribution). We also stained for mismatch repair proteins (MLH1, MSH2, MSH6, PMS2), p53, β-catenin, and p16 and looked for KRAS, BRAF and PIK3CA mutations.
  
  
  RESULTS
  All neoplastic lesions, except 1 lesion, were found in inflamed mucosal areas. Dysplasia was found in 20 of 41 patients with SBA (49%). Dysplasia was flat or raised, low grade or high grade, and adjacent or distant to concomitant SBA. Molecular markers of SBA carcinogenesis complicating CD were similar to those observed in chronic colitis-related colorectal cancer (KRAS, BRAF, p53, MSI), although differences were observed for β-catenin and p16. No PIK3CA mutations were observed.
  
  
  CONCLUSIONS
  These results suggest that there is an inflammation-dysplasia-adenocarcinoma sequence in at least half of CD-related SBA, similar to what is observed in chronic colitis-related colorectal cancer and may have implications for the prevention and treatment of this cancer.
authors.affiliation: 1Department of Pathology, Saint-Antoine Hospital, AP-HP, Hôpitaux Universitaires Est Parisien, Paris, France; 2University Pierre et Marie Curie-Paris 6, Paris, France; 3Intensive Care Unit, Besançon University, CHU of Besançon, Besançon, France; 4Department of Gastroenterology, Saint-Antoine Hospital, AP-HP, Hôpitaux Universitaires Est Parisien, Paris, France; Departments of 5Gastroenterology, and 6Pathology, University Hospitals Leuven, Leuven, Belgium; 7Department of Biochemistry and Oncogenetics, AP-HP, Hôpitaux Universitaires Paris Sud, University Paris Sud, Paul Brousse Hospital, Villlejuif, France; 8Department of Biochemistry, Saint-Antoine Hospital, AP-HP, Hôpitaux Universitaires Est Parisien, Paris, France; Departments of 9Gastroenterology, and 10Pathology, Luigi Sacco Hospital, Milan, Italy; Departments of 11Gastroenterology, and 12Pathology, Rouen University, CHU Charles Nicolle, Rouen, France; 13Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria; 14Department of Pathology, Medical University of Vienna, Vienna, Austria; Departments of 15Gastroenterology, and 16Pathology, Lille University, CHU of Lille, France; Departments of 17Gastroenterology, and 18Pathology, Beaujon Hospital, AP-HP, Université Paris Diderot, France; Departments of 19Gastroenterology, and 20Pathology, CHU of Reims, Université de Reims Champagne-Ardenne, Reims, France; Departments of 21Gastroenterology, and 22Pathology, Cliniques Universitaires UCL de Mont-Godinne, Louvain, Belgium; and 23Department of Gastroenterology, AP-HP, Hôpitaux Universitaires Paris Sud, Site de Bicêtre, University Paris Sud, Le Kremlin-Bicêtre, France.
authors.forename: Magali
authors.initials: M
authors.lastname: Svrcek
authors.forename: Gael
authors.initials: G
authors.lastname: Piton
authors.forename: Jacques
authors.initials: J
authors.lastname: Cosnes
authors.forename: Laurent
authors.initials: L
authors.lastname: Beaugerie
authors.forename: Severine
authors.initials: S
authors.lastname: Vermeire
authors.forename: Karel
authors.initials: K
authors.lastname: Geboes
authors.forename: Antoinette
authors.initials: A
authors.lastname: Lemoine
authors.forename: Pascale
authors.initials: P
authors.lastname: Cervera
authors.forename: Nizar
authors.initials: N
authors.lastname: El-Murr
authors.forename: Sylvie
authors.initials: S
authors.lastname: Dumont
authors.forename: Aurélie
authors.initials: A
authors.lastname: Scriva
authors.forename: Olivier
authors.initials: O
authors.lastname: Lascols
authors.forename: Sandro
authors.initials: S
authors.lastname: Ardizzone
authors.forename: Paolo
authors.initials: P
authors.lastname: Fociani
authors.forename: Guillaume
authors.initials: G
authors.lastname: Savoye
authors.forename: Florence
authors.initials: F
authors.lastname: Le Pessot
authors.forename: Gottfried
authors.initials: G
authors.lastname: Novacek
authors.forename: Fritz
authors.initials: F
authors.lastname: Wrba
authors.forename: Jean-Frédéric
authors.initials: JF
authors.lastname: Colombel
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Leteurtre
authors.forename: Yoram
authors.initials: Y
authors.lastname: Bouhnik
authors.forename: Dominique
authors.initials: D
authors.lastname: Cazals-Hatem
authors.forename: Guillaume
authors.initials: G
authors.lastname: Cadiot
authors.forename: Marie-Danièle
authors.initials: MD
authors.lastname: Diebold
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Rahier
authors.forename: Monique
authors.initials: M
authors.lastname: Delos
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Fléjou
authors.forename: Franck
authors.initials: F
authors.lastname: Carbonnel
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000209:etiology* / Q000401:mortality; D000328:Adult; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000209:etiology* / Q000401:mortality; D003424:Crohn Disease / Q000150:complications*; D005260:Female; D005352:Fibromuscular Dysplasia / Q000175:diagnosis / Q000209:etiology* / Q000401:mortality; D005500:Follow-Up Studies; D006801:Humans; D007249:Inflammation / Q000175:diagnosis / Q000209:etiology* / Q000401:mortality; D007421:Intestine, Small / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012307:Risk Factors; D015996:Survival Rate; D055815:Young Adult