["Field cancerization"--an additional phenomenon in development of colon tumors? K-ras codon 12 mutations in normal colonic mucosa of patients with colorectal neoplasms]

Abstract

Introduction: The c-K-ras2-gene (K-ras) encodes the p21ras protein, which participates in the transduction of mitogenic signals from the cell surface to the nucleus. About 40-50% of colorectal cancers bear a point mutation of the K-ras codon 12 within exon I, leading to activation of the K-ras oncogene.

Methods: Using a polymerase chain reaction (PCR)-based two-step restriction fragment length polymorphism (2sRFLP)-technique, we assessed the frequency of point mutations in the first or second base of K-ras codon 12 in patients suffering from colorectal carcinoma, adenoma, and their normal colon mucosa, respectively.

Results: Similar to other investigators, we found mutations in 7 out of 17 (41%) colorectal carcinomas and 1 out of 4 (25%) adenomas. Using this very sensitive 2sRFLP technique (detection level = 0.2% of mutated cells), we were able to find K-ras codon 12 mutations in normal mucosa in 4 out of 18 (22.2%) patients with colorectal neoplasia.

Conclusions: This result can be explained by the phenomenon of "field cancerization" or by a local micrometastasis of K-ras-positive tumor cells.