Article Text
Abstract
BACKGROUND K-rasmutation is one of the first genetic alterations in classical colorectal carcinogenesis.
AIMS To investigate the role of K-ras mutations in carcinogenesis, in long standing ulcerative colitis.
METHODS A total of 161 microdissected and 100 DNA samples from 13 patients were analysed for K-ras codons 12 and 13 mutations by means of a combination of enriched polymerase chain reaction amplification and temporal temperature gradient electrophoresis.
RESULTS K-rasmutations were found in 21/161 (13%) microdissected samples in 7/13 large bowels (16 and five in codons 12 and 13, respectively), and in 10/100 (10%) mucosal DNA samples (six and four, respectively). One of four patients with six adenocarcinomas had a K-ras mutation in a carcinoma, as well as one of two patients with large dysplasia associated lesion or mass (DALM). Eight of 13 (61%) areas with villous architecture and large, distended goblet cells, had a K-rasmutation, which was significantly more frequent than in low grade dysplasia (one of 23, 4%) but did not reach significance versus high grade dysplasia (four of 14, 28.5%). K-rasmutations were found in one of 20 (5%) flat lesions indefinite for dysplasia, two of 14 (14%) in non-villous, hypermucinous mucosa, and in one of 57 flat areas negative for dysplasia.
CONCLUSION The highest K-ras mutation frequency was found in villous, hypermucinous mucosa. We suggest that this entity should be investigated further as a potential risk lesion for cancer development. It may represent a pathway directly from non-classical dysplasia to cancer, not previously described.
- K-ras mutations
- ulcerative colitis
- dysplasia
- dysplasia associated lesion or mass
Abbreviations used in this paper
- DALM
- dysplasia associated lesion or mass
- PCR
- polymerase chain reaction
- TTGE
- temporal temperature gradient electrophoresis
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Abbreviations used in this paper
- DALM
- dysplasia associated lesion or mass
- PCR
- polymerase chain reaction
- TTGE
- temporal temperature gradient electrophoresis