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

Sun M. Chung, Jean Kao, Elizabeth Hyjek, Yao Tseng Chen

Research output: Contribution to journalArticle

15 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1351-1355
Number of pages5
JournalInternational Journal of Oncology
Volume31
Issue number6
StatePublished - Dec 2007
Externally publishedYes

Fingerprint

Barrett Esophagus
Mutation Rate
Adenocarcinoma
Alleles
Mutation
Laser Capture Microdissection
Esophagectomy
DNA Sequence Analysis
Exons
Immunohistochemistry
Staining and Labeling
Polymerase Chain Reaction
DNA

Keywords

  • Barrett's esophagus
  • Laser microdissection
  • p53

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

p53 in esophageal adenocarcinoma : A critical reassessment of mutation frequency and identification of 72Arg as the dominant allele. / Chung, Sun M.; Kao, Jean; Hyjek, Elizabeth; Chen, Yao Tseng.

In: International Journal of Oncology, Vol. 31, No. 6, 12.2007, p. 1351-1355.

Research output: Contribution to journalArticle

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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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