Original ResearchBasic and Translational—Alimentary TractField Cancerization in the Intestinal Epithelium of Patients With Crohn's Ileocolitis
Section snippets
Patients and Methods
See Supplementary Materials and Methods for full methods.
Results
Somatic mutations in TP53, CDKN2A, or KRAS were detected in neoplastic tissue from 7 of 10 patients (Table 1). Individual histologically normal, inflamed, or dysplastic crypts, cancer glands, or small areas of poorly differentiated tumor (∼500 cells) were then microdissected from multiple tissue samples from each patient with detected mutations and genotyped for the somatic mutation(s) detected in the patient’s neoplasia (Supplementary Table 3).
Discussion
The genetic and histologic mechanisms driving the development of CD-associated cancers have not been conclusively determined. The data presented herein are strong evidence that field cancerization, the replacement of the normal epithelium with a protumorigenic clone,8, 9 before any dysplastic histologic change contributes to carcinogenesis in patients with CD. In 5 of 7 informative patients with neoplasia, the same point mutation in KRAS, CDKN2A, or TP53 could be detected within the tumor,
Acknowledgments
Trevor A. Graham's present address is: Center for Evolution and Cancer, University of California, San Francisco, 2340 Sutter Street, Box 1351, San Francisco, California 94143.
The authors thank members of the Equipment Park and Experimental Histopathology Laboratories at the Cancer Research UK London Research Institute for technical assistance.
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2021, Human PathologyCitation Excerpt :For instance, in sporadic colorectal adenocarcinoma, TP53 mutations are a late genomic event and are unusual in adenomatous precursor neoplasms [29,30]. Conversely, TP53 mutations in IBD-associated colorectal adenocarcinoma are an early event and typically found in not only precancerous neoplasms but also the non-neoplastic colonic mucosa [31–33]. In fact, identical mutations in TP53 were previously reported to be detected within matched non-neoplastic and dysplastic colorectal specimens from the same IBD patient, supporting the concept of field cancerization in the development of IBD-associated colorectal adenocarcinoma [32].
Conflicts of interest The authors disclose no conflicts.
Funding S.G. received funding from the Price Institute of Surgical Research, University of Louisville, and Sarah Shallenberger Brown and support in part from National Institutes of Health/National Institute of Environmental Health Sciences grant 1P30ES014443-01A1. T.A.G., R.J., S.J.L., and N.A.W. were supported by Cancer Research UK. M.R.-J. is supported by UCLH/UCL Comprehensive Biomedical Research Centre. T.A.G. and M.R.-J. received funding for this study from the University College London Hospitals Charities - Fast Track Grant.