Analysis of Ki-ras and p53 gene mutations in laterally spreading tumors of the colorectum.

Abstract

A laterally spreading tumor (LST) is considered to be a specific subtype of superficial colorectal tumors, in view of its characteristic clinicopathological features. We attempted to compare genetic alterations found in LST (>10 mm) with those found in IIa-type adenomas (10 mm or less (small superficial elevated lesion)) and conventional polypoid adenomas (>10 mm). In addition, multiple sampling by microdissection was performed for 14 LST to examine genetic heterogeneity in the Ki-ras and p53 gene mutation patterns. Polymerase chain reaction, single-strand conformation polymorphism and direct sequencing were used to analyze Ki-ras and p53 gene mutations in 73 sporadic colorectal adenomas: 28 LST; 22 IIa-type adenomas; and 23 polypoid adenomas. Ki-ras gene mutations were found more frequently in LST (6/28 tumors) and polypoid adenomas (6/23 tumors) than in IIa-type adenomas (2/22 tumors), although this difference was not statistically significant. The frequency of p53 gene mutations in the 28 LST was 25% (7/28), which was significantly higher than that found in IIa-type adenomas (P < 0.05). However, although p53 gene mutations were found more frequently in LST than in polypoid adenomas, this difference was not statistically significant. Seven LST exhibited a combination of wild-type and mutant-type tumor cells having the p53 gene mutation pattern, whereas a pattern of different Ki-ras gene mutations was found in two of three LST that exhibited Ki-ras gene mutation heterogeneity. We suggest that the LST exhibited a characteristic pattern in terms of the Ki-ras as well as the p53 gene mutation pattern, thereby supporting the hypothesis that LST is a specific subtype of colorectal tumors.