Cancer  2002 Jan 1;94(1):219-27 

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

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

Second Department of Internal Medicine, Shinshu University School of Medicine,
Matsumoto, Nagano, Japan.

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. Copyright 2002 American Cancer Society.

PMID: 11815980 [PubMed - indexed for MEDLINE]