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Hypermethylated APC DNA in plasma and prognosis of patients with esophageal adenocarcinoma.

Publication ,  Journal Article
Kawakami, K; Brabender, J; Lord, RV; Groshen, S; Greenwald, BD; Krasna, MJ; Yin, J; Fleisher, AS; Abraham, JM; Beer, DG; Sidransky, D; Eads, C ...
Published in: J Natl Cancer Inst
November 15, 2000

BACKGROUND: The adenomatous polyposis coli (APC) locus on chromosome 5q21-22 shows frequent loss of heterozygosity (LOH) in esophageal carcinomas. However, the prevalence of truncating mutations in the APC gene in esophageal carcinomas is low. Because hypermethylation of promoter regions is known to affect several other tumor suppressor genes, we investigated whether the APC promoter region is hypermethylated in esophageal cancer patients and whether this abnormality could serve as a prognostic plasma biomarker. METHODS: We assayed DNA from tumor tissue and matched plasma from esophageal cancer patients for hypermethylation of the promoter region of the APC gene. We used the maximal chi-square statistic to identify a discriminatory cutoff value for hypermethylated APC DNA levels in plasma and used bootstrap-like simulations to determine the P: value to test for the strength of this association. This cutoff value was used to generate Kaplan-Meier survival curves. All P values were based on two-sided tests. RESULTS: Hypermethylation of the promoter region of the APC gene occurred in abnormal esophageal tissue in 48 (92%) of 52 patients with esophageal adenocarcinoma, in 16 (50%) of 32 patients with esophageal squamous cell carcinoma, and in 17 (39.5%) of 43 patients with Barrett's metaplasia but not in matching normal esophageal tissues. Hypermethylated APC DNA was observed in the plasma of 13 (25%) of 52 adenocarcinoma patients and in two (6.3%) of 32 squamous carcinoma patients. High plasma levels of methylated APC DNA were statistically significantly associated with reduced patient survival (P =.016). CONCLUSION: The APC promoter region was hypermethylated in tumors of the majority of patients with primary esophageal adenocarcinomas. Levels of hypermethylated APC gene DNA in the plasma may be a useful biomarker of biologically aggressive disease in esophageal adenocarcinoma patients and should be evaluated as a potential biomarker in additional tumor types.

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Published In

J Natl Cancer Inst

DOI

ISSN

0027-8874

Publication Date

November 15, 2000

Volume

92

Issue

22

Start / End Page

1805 / 1811

Location

United States

Related Subject Headings

  • Survival Analysis
  • Promoter Regions, Genetic
  • Prognosis
  • Precancerous Conditions
  • Polymerase Chain Reaction
  • Oncology & Carcinogenesis
  • Methylation
  • Loss of Heterozygosity
  • Humans
  • Gastric Mucosa
 

Citation

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Kawakami, K., Brabender, J., Lord, R. V., Groshen, S., Greenwald, B. D., Krasna, M. J., … Meltzer, S. J. (2000). Hypermethylated APC DNA in plasma and prognosis of patients with esophageal adenocarcinoma. J Natl Cancer Inst, 92(22), 1805–1811. https://doi.org/10.1093/jnci/92.22.1805
Kawakami, K., J. Brabender, R. V. Lord, S. Groshen, B. D. Greenwald, M. J. Krasna, J. Yin, et al. “Hypermethylated APC DNA in plasma and prognosis of patients with esophageal adenocarcinoma.J Natl Cancer Inst 92, no. 22 (November 15, 2000): 1805–11. https://doi.org/10.1093/jnci/92.22.1805.
Kawakami K, Brabender J, Lord RV, Groshen S, Greenwald BD, Krasna MJ, et al. Hypermethylated APC DNA in plasma and prognosis of patients with esophageal adenocarcinoma. J Natl Cancer Inst. 2000 Nov 15;92(22):1805–11.
Kawakami, K., et al. “Hypermethylated APC DNA in plasma and prognosis of patients with esophageal adenocarcinoma.J Natl Cancer Inst, vol. 92, no. 22, Nov. 2000, pp. 1805–11. Pubmed, doi:10.1093/jnci/92.22.1805.
Kawakami K, Brabender J, Lord RV, Groshen S, Greenwald BD, Krasna MJ, Yin J, Fleisher AS, Abraham JM, Beer DG, Sidransky D, Huss HT, Demeester TR, Eads C, Laird PW, Ilson DH, Kelsen DP, Harpole D, Moore MB, Danenberg KD, Danenberg PV, Meltzer SJ. Hypermethylated APC DNA in plasma and prognosis of patients with esophageal adenocarcinoma. J Natl Cancer Inst. 2000 Nov 15;92(22):1805–1811.
Journal cover image

Published In

J Natl Cancer Inst

DOI

ISSN

0027-8874

Publication Date

November 15, 2000

Volume

92

Issue

22

Start / End Page

1805 / 1811

Location

United States

Related Subject Headings

  • Survival Analysis
  • Promoter Regions, Genetic
  • Prognosis
  • Precancerous Conditions
  • Polymerase Chain Reaction
  • Oncology & Carcinogenesis
  • Methylation
  • Loss of Heterozygosity
  • Humans
  • Gastric Mucosa