J Gastroenterol Hepatol  2000 Oct;15(10):1151-7 

Analysis of K-ras codon 12 mutations and p53 overexpression in colorectal
nodule-aggregating tumors.

Kusaka T, Fukui H, Sano Y, Ueda Y, Chiba T, Fujimori T.

Department of Pathology, Dokkyo University School of Medicine, Shimotsuga,
Tochigi, Japan.

BACKGROUND AND AIMS: Morphologically, colorectal nodule-aggregating tumors are
quite different from polypoid-type colorectal tumors that develop via the
adenoma-carcinoma sequence. Although polypoid-type colorectal tumors are well
known to have a high incidence of K-ras gene mutation and p53 overexpression,
colorectal nodule-aggregating tumors have not been examined in terms of genetic
changes and clinicopathological features. In the present study, therefore, we
analysed the clinicopathological features, genetic changes in K-ras codon 12,
and p53 overexpression in colorectal nodule-aggregating tumors. METHODS: A total
of 18 colorectal nodule-aggregating tumors were surgically resected and then
analysed clinicopathologically. Immunohistochemistry and polymerase chain
reaction-single stranded conformational polymorphism were performed to analyse
p53 abnormalities in the tumors. K-ras codon 12 mutations were screened out by
the polymerase chain reaction-restriction fragment length polymorphism method
and analysed by fluorescence direct sequencing. RESULTS: p53 overexpression was
observed in six lesions (33%). p53-overexpressing cells were observed in parts
of carcinoma or adenoma showing high-grade atypia. Four of the 10 (40%) samples
had a p53 gene mutation. Nine of the 18 (50%) samples had a K-ras codon 12 point
mutation. In eight cases (89%), the mutations of the K-ras codon 12 were of the
same type: GGT (glycine) to GTT (valine). CONCLUSIONS: The colorectal
nodule-aggregating tumor has distinctive characteristics showing a morphological
phenotype of the superficial-type tumors and genotype of the polypoid tumors in
terms of K-ras gene mutation and p53 overexpression.

PMID: 11106095 [PubMed - indexed for MEDLINE]