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

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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.

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Acknowledgments

We thank Kristin Bergethon and Clarice Bo-Moon Chang for their excellent technical assistance. We also thank Dr. Badizadegan, Dr. Deshpande, Dr. Mino-Kenudson, and Dr. Zukerberg for their thoughtful discussions.

Author’s contribution

JKL, LPL, AS, DYP, and JHC conceived and carried out experiments; JB, JYH, KF, DDS, and DRB carried out experiments and analyzed data; RDO, AJI, and GYL conceived experiments and analyzed data; KWJV, CS, BES, JRK, and HK analyzed data; JKL, KWJV, HK, AJI, and GYL assembled the data; and all authors were involved in data interpretation. JKL, AJI, and GYL wrote the paper, and all authors had final approval of the submitted and published versions.

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    Authors and Affiliations

    1. Department of Pathology, Massachusetts General Hospital/Harvard Medical School, Boston, MA, 02116, USA

      Jochen K. Lennerz, Long Phi Le, Julie M. Batten, Jae Young Han, Kenneth C. Fan, A John Iafrate & Gregory Y. Lauwers

    2. Division of Gastroenterology, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA

      Kimberley W. J. van der Sloot, Dora Dias-Santagata & Hamed Khalili

    3. M.D. Anderson Cancer Center, School of Health Professions, The University of Texas, Houston, TX, USA

      Jae Young Han

    4. Dartmouth-Hitchcock Inflammatory Bowel Disease Center, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA

      Corey A. Siegel

    5. Department of Pathology, Brigham and Women’s Hospital, Boston, MA, USA

      Amitabh Srivastava & Robert D. Odze

    6. Department of Pathology, Pusan National University Hospital and Pusan National University School of Medicine, Busan, Republic of Korea

      Do Youn Park

    7. Swedish Medical Center, CellNetix Pathology and Laboratories, Seattle, WA, USA

      Jey-Hsin Chen

    8. Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA

      Bruce E. Sands

    9. Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women’s Hospital, Boston, MA, USA

      Joshua R. Korzenik

    10. Department of Hematology/Oncology, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA

      Darrell R. Borger

    11. Clinical and Translational Epidemiology Unit, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA

      Hamed Khalili

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    1. Jochen K. Lennerz
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    Correspondence to Jochen K. Lennerz.

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    All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. For this type of study, formal consent is not required.

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    A John Iafrate and Gregory Y. Lauwers contributed equally to this work.

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    Supplemental methods and 4 supplemental tables (details of antibodies, immunophenotype, literature reviewed, and clinicopathological features by genetic subgroup) (DOC 176 kb)

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    Lennerz, J.K., van der Sloot, K.W.J., Le, L.P. et al. Colorectal cancer in Crohn’s colitis is comparable to sporadic colorectal cancer. Int J Colorectal Dis 31, 973–982 (2016). https://doi.org/10.1007/s00384-016-2574-x

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