Sn. Andersen et al., Villous, hypermucinous mucosa in long standing ulcerative colitis shows high frequency of K-ras mutations, GUT, 45(5), 1999, pp. 686-692
Background-K-ras mutation is one of the first genetic alterations in classi
cal colorectal carcinogenesis.
Aims-To investigate the Pole of K-ras mutations in carcinogenesis, in long
standing ulcerative colitis.
Method-A total of 161 microdissected and 100 DNA samples from 13 patients w
ere analysed for K-ras codons 12 and 13 mutations by means of a combination
of enriched polymerase chain reaction amplification and temporal temperatu
re gradient electrophoresis.
Results-K-ras mutations were found in 21/161 (13%) microdissected samples i
n 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, disten
ded goblet cells, had a K-ras mutation, which was significantly more freque
nt than in low grade dysplasia (one of 23, 4%) but did not reach significan
ce versus high grade dysplasia (four of 14, 28.5%). K-ras mutations were fo
und 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 negativ
e for dysplasia.
Conclusion-The highest K-ras mutation frequency was found in villous, hyper
mucinous mucosa. We suggest that this entity should be investigated further
as a potential risk lesion for cancer development. It may represent a path
way directly from non-classical dysplasia to cancer, not previously describ
ed.