title: 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.
authors.affiliation: Second Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto, Nagano, Japan.
authors.forename: Shigetoshi
authors.initials: S
authors.lastname: Hosaka
authors.forename: Yuji
authors.initials: Y
authors.lastname: Aoki
authors.forename: Taiji
authors.initials: T
authors.lastname: Akamatsu
authors.forename: Naoshi
authors.initials: N
authors.lastname: Nakamura
authors.forename: Noriko
authors.initials: N
authors.lastname: Hosaka
authors.forename: Kendo
authors.initials: K
authors.lastname: Kiyosawa
mesh_terms: D000236:Adenoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D016158:Genes, p53; D011905:Genes, ras; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D016159:Tumor Suppressor Protein p53