K-ras mutations in colorectal polyps: site, histology and size do matter.

GL Williams MB BCh,FRCS a,b; GJS Jenkins PhD b; J Beynon MB BS,MS,FRCS a JM Parry PhD DSc b

a Department of Surgery, Singleton Hospital, Swansea, UK. b School of Biological Sciences, Swansea University, Swansea, UK.

AIM: Mutation of the oncogene K-ras is thought to be important in the multistep progression to colorectal cancer. K-ras is involved in the cell signaling pathway and a mutation will cause uncontrolled cell proliferation. The aim of our study was to assess the relationship between K-ras mutations and various characteristics of colorectal polyps including site, size and histology. METHODS: Polyps were collected during colonoscopy from 55 successive patients and control tissue obtained from 20 other patients. DNA was extracted from the fresh tissue. Primers were designed to amplify the regions including codons 12 and 13 during PCR. Following restriction enzyme digestion with mva1, mutations were confirmed by sequencing. RESULTS: 21% of the 55 polyps had a mutation of K-ras at codon 12. None of the controls had mutations. Of the 15 rectal polyps 33% had a mutation, whereas only 18% of the 40 colonic polyps had none. 36 polyps were <1cm (mutation rate 8%) and 19 polyps were >1cm (mutation rate 47%). Histological type revealed that 30% villous/tubulovillous polyps had a mutation, compared to much lower rates of K-ras mutations in tubular (9%) and metaplastic polyps (0). No difference in mutation rate was found in varying grades of dysplasia in our study. CONCLUSIONS: This small study reveals that K-ras mutations in our population tended to be associated with polyps found in the rectum, having a larger size and villous histology. Further studies are needed to understand fully the importance of this oncogene in the progression of some polyps and their different characteristics to carcinoma.

KEY WORDS: colorectal, polyps, K-ras mutations.

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Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Molecular Pathology.