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Detection of genetic alterations in the p53 suppressor gene and the K-ras oncogene among different grades of dysplasia in patients with colorectal adenomas.

Abstract：

BACKGROUND:Although it is believed that p53 suppressor gene mutations, compared with mutations in the K-ras oncogene, occur at a later stage of colorectal tumorigenesis, the distribution of these genetic alterations at an early stage remains poorly characterized. METHODS:The authors analyzed the immunoreactivity for p53 protein (p53 protein expression), which reflects the functionally altered p53 gene, and K-ras mutations at codons 12 in 68 colorectal adenomas with both low-grade and high-grade dysplasia obtained from 62 patients. RESULTS:The prevalence of p53 positive immunostaining was significantly greater compared with the prevalence of K-ras mutations both in low-grade dysplasia and in high-grade dysplasia. Twenty-two adenomas (32.3%) showed positive immunostaining for p53 protein in high-grade dysplasia and also were positive for p53 in surrounding low-grade dysplastic tissues; 20 adenomas (29.4%) showed positive immunostaining for p53 protein in high-grade dysplasia and were negative for p53 in surrounding low-grade dysplastic tissues; 8 adenomas (11.7%) showed negative immunostaining for p53 protein in high-grade dysplasia and were positive for p53 in surrounding low-grade dysplastic tissues; and 18 adenomas (26.4%) showed negative immunostaining for p53 protein in both high-grade dysplasia and in surrounding low-grade dysplastic tissues. On the whole, a significant difference (P < 0.05) was seen in the frequency of p53 positive immunostaining between low-grade dysplasia and high-grade dysplasia (44.1% and 61.8%, respectively) but not in that of K-ras mutations (20.3% and 23.4%, respectively). CONCLUSIONS:The results of this study suggest that mutation of the p53 suppressor gene occurs earlier in the adenoma-carcinoma sequence than K-ras mutation, providing a clue for further understanding of the role of the p53 gene in the early stage of colorectal tumorigenesis.

journal_name

Cancer

journal_title

Cancer

authors

Hosaka S,Aoki Y,Akamatsu T,Nakamura N,Hosaka N,Kiyosawa K

doi

10.1002/cncr.10198

subject

Has Abstract

pub_date

2002-01-01 00:00:00

pages

219-27

issue

eissn

0008-543X

issn

1097-0142

pii

10.1002/cncr.10198

journal_volume

pub_type

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Detection of genetic alterations in the p53 suppressor gene and the K-ras oncogene among different grades of dysplasia in patients with colorectal adenomas.