p53 in esophageal adenocarcinoma: A critical reassessment of mutation frequency and identification of 72Arg as the dominant allele

  • Authors:
    • Sun M. Chung
    • Jean Kao
    • Elizabeth Hyjek
    • Yao-Tseng Chen
  • View Affiliations

  • Published online on: December 1, 2007     https://doi.org/10.3892/ijo.31.6.1351
  • Pages: 1351-1355
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Abstract

p53 alterations have been implicated in the progression of Barrett's esophagus to esophageal adenocarcinoma. However, the wide range of reported p53 alteration frequencies in esophageal adenocarcinoma makes using p53 as a marker of malignant transformation of Barrett's esophagus problematic. To determine the utility of p53 in Barrett's esophagus monitoring, the frequency of p53 alteration was critically reassessed using esophagectomy specimens of 40 cases of esophageal adenocarcinoma, including 10 with Barrett's esophagus and high-grade dysplasia, 8 with low-grade dysplasia and 7 with no dysplasia. DNA was extracted from tumor cells isolated by laser capture microdissection to maximize the assay sensitivity and mutations in exons 4-8 of p53 were determined by PCR direct sequencing. Mutations in p53 were identified in 75% (30/40) of the esophageal adenocarcinoma. p53 protein overexpression, detected by immunohistochemistry, was found in 58% (23/40) of the esophageal adenocarcinoma, 60% (6/10) of Barrett's esophagus with high-grade dysplasia, 12% (1/8) of Barrett's esophagus with low-grade dysplasia, and 0% of Barrett's esophagus without dysplasia. In addition to the mutations, a predominance of the 72Arg allele (89% homozygous) was found over the 72Pro allele in this series. p53 mutation frequency in this study was higher than reported in most of the literature and DNA sequencing detected more p53 alterations than immunohistochemical staining. However, p53 appeared to be a late marker in the neoplastic transformation, and no p53 change was found in ≈25% of the adenocarcinoma. We concluded that p53 is insufficient as a single marker for Barrett's esophagus monitoring but may be useful as part of a panel due to its high specificity.

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December 2007
Volume 31 Issue 6

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Chung SM, Kao J, Hyjek E and Chen Y: p53 in esophageal adenocarcinoma: A critical reassessment of mutation frequency and identification of 72Arg as the dominant allele. Int J Oncol 31: 1351-1355, 2007
APA
Chung, S.M., Kao, J., Hyjek, E., & Chen, Y. (2007). p53 in esophageal adenocarcinoma: A critical reassessment of mutation frequency and identification of 72Arg as the dominant allele. International Journal of Oncology, 31, 1351-1355. https://doi.org/10.3892/ijo.31.6.1351
MLA
Chung, S. M., Kao, J., Hyjek, E., Chen, Y."p53 in esophageal adenocarcinoma: A critical reassessment of mutation frequency and identification of 72Arg as the dominant allele". International Journal of Oncology 31.6 (2007): 1351-1355.
Chicago
Chung, S. M., Kao, J., Hyjek, E., Chen, Y."p53 in esophageal adenocarcinoma: A critical reassessment of mutation frequency and identification of 72Arg as the dominant allele". International Journal of Oncology 31, no. 6 (2007): 1351-1355. https://doi.org/10.3892/ijo.31.6.1351