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Colon carcinogenesis in inflammatory bowel disease
S H Itzkowitz1, B Greenwald, S J Meltzer
1Department of Medicine, Mount Sinai School of Medicine, New York City, New York; and Departments of *Medicine, and †Pathology, Oncology, and Molecular Biology, University of Maryland School of Medicine, Baltimore, Maryland, U.S.A.
Inflammatory Bowel Diseases
|January 4, 2013
Summary
Colon cancers in inflammatory bowel disease (IBD) show distinct molecular changes compared to sporadic cancers. Understanding these differences in colitis-associated neoplasms is key for improved patient management.
Area of Science:
- Gastroenterology
- Oncology
- Molecular Biology
Background:
- Colitis-associated neoplasms share some features with sporadic colon cancers, but molecular alterations are less understood.
- Phenotypic changes like increased sialomucin and decreased sialic acid O-acetylation correlate with malignant progression in IBD.
Purpose of the Study:
- To investigate the molecular and genetic alterations in colitis-associated colon neoplasms.
- To compare these alterations with those found in sporadic colon carcinogenesis.
Main Methods:
- Analysis of phenotypic alterations including mucin expression and sialic acid O-acetylation.
- Assessment of molecular genetic changes such as genomic instability, aneuploidy, protooncogene activation, and tumor suppressor gene mutations.
Main Results:
- Increased sialomucin and decreased sialic acid O-acetylation suggest small intestinal metaplasia during carcinogenesis.
- Genomic instability and aneuploidy are associated with malignant progression.
- Activation of k-ras, c-src and alterations in p53, APC genes occur, with potentially different timing than in sporadic cancers. Microsatellite instability is present, but mismatch repair gene mutations are not yet described.
Conclusions:
- Colitis-associated carcinogenesis involves distinct molecular and genetic pathways.
- Further research is needed to fully understand the pathobiology and guide clinical management of IBD-associated colon cancer.
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