Colorectal cancer in Crohn’s colitis is comparable to sporadic colorectal cancer

• Published in: International journal of colorectal disease Vol. 31; no. 5; pp. 973 - 982
• Main Authors: Lennerz, Jochen K., van der Sloot, Kimberley W. J., Le, Long Phi, Batten, Julie M., Han, Jae Young, Fan, Kenneth C., Siegel, Corey A., Srivastava, Amitabh, Park, Do Youn, Chen, Jey-Hsin, Sands, Bruce E., Korzenik, Joshua R., Odze, Robert D., Dias-Santagata, Dora, Borger, Darrell R., Khalili, Hamed, Iafrate, A John, Lauwers, Gregory Y.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.05.2016; Springer; Springer Nature B.V
• Subjects: Adult; Aged; Analysis; Colitis; Colorectal cancer; Colorectal Neoplasms - complications; Colorectal Neoplasms - genetics; Crohn Disease - complications; Crohn Disease - pathology; DNA Methylation - genetics; Female; Follow-Up Studies; Gastroenterology; Genetic Association Studies; GTP Phosphohydrolases - genetics; Health aspects; Hepatology; Humans; Immunophenotyping; Internal Medicine; Male; Medicine; Medicine & Public Health; Membrane Proteins - genetics; Microsatellite Repeats - genetics; Middle Aged; Mutation; MutL Protein Homolog 1 - genetics; Original Article; Proctology; Promoter Regions, Genetic - genetics; Proto-Oncogene Proteins B-raf - genetics; Proto-Oncogene Proteins p21(ras) - genetics; Surgery; Survival Analysis; Targeted re-sequencing; SNaPshot; Colorectal cancer; Crohn’s colitis
• ISSN: 0179-1958; 1432-1262
• DOI: 10.1007/s00384-016-2574-x

Purpose 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. Methods 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. Results 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). Conclusion In summary, the clinicopathological and molecular profile of CD-associated CRC is similar to that observed in sporadic CRC.