Villous, hypermucinous mucosa in long standing ulcerative colitis shows high frequency of K-ras mutations.
BACKGROUND
K-ras mutation is one of the first genetic alterations in classical colorectal carcinogenesis.


OBJECTIVE
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-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.


CONCLUSIONS
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.
Andersen
S N
SN
Institute of Forensic Medicine, The National Hospital, University of Oslo, Norway.
Lovig
T
T
Clausen
O P
OP
Bakka
A
A
Fausa
O
O
Rognum
T O
TO
D000230:Adenocarcinoma / Q000235:genetics; D000328:Adult; D000368:Aged; D003093:Colitis, Ulcerative / Q000235:genetics* / Q000473:pathology; D003110:Colonic Neoplasms / Q000235:genetics; D005260:Female; D011905:Genes, ras; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012307:Risk Factors