Villous, hypermucinous mucosa in long standing ulcerative colitis shows high frequency of K-ras mutations

• Published in: Gut 1999-11, Vol.45 (5), p.686-692
• Main Authors: ANDERSEN, S. N, LØVIG, T, CLAUSEN, O. P. F, BAKKA, A, FAUSA, O, ROGNUM, T. O
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - genetics; Adult; Aged; Biological and medical sciences; Colitis, Ulcerative - genetics; Colitis, Ulcerative - pathology; Colonic Neoplasms - genetics; Digestive system; Female; Genes, ras; Humans; Intestinal Mucosa - metabolism; Intestinal Mucosa - pathology; Investigative techniques, diagnostic techniques (general aspects); Male; Medical sciences; Middle Aged; Mutation; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Risk Factors
• ISSN: 0017-5749; 1468-3288; 1458-3288
• DOI: 10.1136/gut.45.5.686

K-ras mutation is one of the first genetic alterations in classical colorectal carcinogenesis. To investigate the role of K-ras mutations in carcinogenesis, in long standing ulcerative colitis. 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. K-ras mutations 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-ras mutation, 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-ras mutations 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. 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.