title: Colorectal cancer in Crohn's colitis is comparable to sporadic colorectal cancer.
abstract: It is now recognized that Crohn's disease (CD), similar to ulcerative colitis (UC), carries an up to 20-fold higher cancer risk, and the development of colorectal carcinoma (CRC) is a major long-term complication. Once CRC is present, molecular profiling is one of the components in selecting appropriate treatment strategies; however, in contrast to UC, genetic alterations in Crohn's colitis-associated CRC are poorly understood.
  
  
  
  In a series of 227 patients with Crohn's colitis, we identified 33 cases of CRC (~14 %) and performed targeted mutational analysis of BRAF/KRAS/NRAS and determined microsatellite status as well as immunophenotype of the tumors.
  
  
  
  In the CRC cohort, the median age at time of cancer diagnosis was 58 (range 34-77 vs. 59.5 in sporadic; P = 0.81) and the median CD duration was 29 years (range 6-45). As a group, CRC complicating Crohn's colitis is BRAF (97 %) and NRAS (100 %) wild type and the vast majority is microsatellite stable (94 %); KRAS-mutations were found in six cases (18 %). Stage grouping, anatomic distribution, and overall survival were similar to sporadic CRC; however, long-standing CD (≥25 years) as well as gastric-immunophenotype (MUC5AC+) was associated with significantly shorter overall survival (P = 0.0029; P = 0.036, respectively).
  
  
  
  In summary, the clinicopathological and molecular profile of CD-associated CRC is similar to that observed in sporadic CRC.
authors.affiliation: Department of Pathology, Massachusetts General Hospital/Harvard Medical School, Boston, MA, 02116, USA. JLennerz@partners.org.
authors.forename: Jochen K
authors.initials: JK
authors.lastname: Lennerz
authors.affiliation: Division of Gastroenterology, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA.
authors.forename: Kimberley W J
authors.initials: KWJ
authors.lastname: van der Sloot
authors.affiliation: Department of Pathology, Massachusetts General Hospital/Harvard Medical School, Boston, MA, 02116, USA.
authors.forename: Long Phi
authors.initials: LP
authors.lastname: Le
authors.affiliation: Department of Pathology, Massachusetts General Hospital/Harvard Medical School, Boston, MA, 02116, USA.
authors.forename: Julie M
authors.initials: JM
authors.lastname: Batten
authors.affiliation: Department of Pathology, Massachusetts General Hospital/Harvard Medical School, Boston, MA, 02116, USA.|M.D. Anderson Cancer Center, School of Health Professions, The University of Texas, Houston, TX, USA.
authors.forename: Jae Young
authors.initials: JY
authors.lastname: Han
authors.affiliation: Department of Pathology, Massachusetts General Hospital/Harvard Medical School, Boston, MA, 02116, USA.
authors.forename: Kenneth C
authors.initials: KC
authors.lastname: Fan
authors.affiliation: Dartmouth-Hitchcock Inflammatory Bowel Disease Center, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA.
authors.forename: Corey A
authors.initials: CA
authors.lastname: Siegel
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA.
authors.forename: Amitabh
authors.initials: A
authors.lastname: Srivastava
authors.affiliation: Department of Pathology, Pusan National University Hospital and Pusan National University School of Medicine, Busan, Republic of Korea.
authors.forename: Do Youn
authors.initials: DY
authors.lastname: Park
authors.affiliation: Swedish Medical Center, CellNetix Pathology and Laboratories, Seattle, WA, USA.
authors.forename: Jey-Hsin
authors.initials: JH
authors.lastname: Chen
authors.affiliation: Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Bruce E
authors.initials: BE
authors.lastname: Sands
authors.affiliation: Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women's Hospital, Boston, MA, USA.
authors.forename: Joshua R
authors.initials: JR
authors.lastname: Korzenik
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA.
authors.forename: Robert D
authors.initials: RD
authors.lastname: Odze
authors.affiliation: Division of Gastroenterology, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA.
authors.forename: Dora
authors.initials: D
authors.lastname: Dias-Santagata
authors.affiliation: Department of Hematology/Oncology, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA.
authors.forename: Darrell R
authors.initials: DR
authors.lastname: Borger
authors.affiliation: Division of Gastroenterology, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA.|Clinical and Translational Epidemiology Unit, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA.
authors.forename: Hamed
authors.initials: H
authors.lastname: Khalili
authors.affiliation: Department of Pathology, Massachusetts General Hospital/Harvard Medical School, Boston, MA, 02116, USA.
authors.forename: A John
authors.initials: AJ
authors.lastname: Iafrate
authors.affiliation: Department of Pathology, Massachusetts General Hospital/Harvard Medical School, Boston, MA, 02116, USA.
authors.forename: Gregory Y
authors.initials: GY
authors.lastname: Lauwers
mesh_terms: D000328:Adult; D000368:Aged; D015179:Colorectal Neoplasms / Q000150:complications* / Q000235:genetics; D003424:Crohn Disease / Q000150:complications* / Q000473:pathology; D019175:DNA Methylation / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D020558:GTP Phosphohydrolases / Q000235:genetics; D056726:Genetic Association Studies; D006801:Humans; D016130:Immunophenotyping; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged; D000070957:MutL Protein Homolog 1 / Q000235:genetics; D009154:Mutation; D011401:Promoter Regions, Genetic / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D016019:Survival Analysis
chemical_list: C117307:KRAS protein, human; C501486:MLH1 protein, human; D008565:Membrane Proteins; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D020558:GTP Phosphohydrolases; C579846:NRAS protein, human; D000070957:MutL Protein Homolog 1; D016283:Proto-Oncogene Proteins p21(ras)
keywords: Colorectal cancer; Crohn’s colitis; SNaPshot; Targeted re-sequencing