Jochen K Lennerz1, Kimberley W J van der Sloot2, Long Phi Le3, Julie M Batten3, Jae Young Han3,4, Kenneth C Fan3, Corey A Siegel5, Amitabh Srivastava6, Do Youn Park7, Jey-Hsin Chen8, Bruce E Sands9, Joshua R Korzenik10, Robert D Odze6, Dora Dias-Santagata2, Darrell R Borger11, Hamed Khalili2,12, A John Iafrate3, Gregory Y Lauwers3. 1. Department of Pathology, Massachusetts General Hospital/Harvard Medical School, Boston, MA, 02116, USA. JLennerz@partners.org. 2. Division of Gastroenterology, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA. 3. Department of Pathology, Massachusetts General Hospital/Harvard Medical School, Boston, MA, 02116, USA. 4. M.D. Anderson Cancer Center, School of Health Professions, The University of Texas, Houston, TX, USA. 5. Dartmouth-Hitchcock Inflammatory Bowel Disease Center, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA. 6. Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA. 7. Department of Pathology, Pusan National University Hospital and Pusan National University School of Medicine, Busan, Republic of Korea. 8. Swedish Medical Center, CellNetix Pathology and Laboratories, Seattle, WA, USA. 9. Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA. 10. Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women's Hospital, Boston, MA, USA. 11. Department of Hematology/Oncology, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA. 12. Clinical and Translational Epidemiology Unit, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA.
Abstract
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.
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.
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