Aberrant vimentin methylation is characteristic of upper gastrointestinal pathologies - PubMed (original) (raw)

Comparative Study

Aberrant vimentin methylation is characteristic of upper gastrointestinal pathologies

Helen Moinova et al. Cancer Epidemiol Biomarkers Prev. 2012 Apr.

Abstract

Background: We have previously established aberrant DNA methylation of vimentin exon-1 (VIM methylation) as a common epigenetic event in colon cancer and as a biomarker for detecting colon neoplasia. We now examine vimentin methylation in neoplasia of the upper gastrointestinal tract.

Methods: Using a quantitative real-time methylation-specific PCR assay, we tested for vimentin methylation in archival specimens of esophageal and gastric neoplasia.

Results: We find that acquisition of aberrant vimentin methylation is highly common in these neoplasms, but largely absent in controls. The highest frequency of vimentin methylation was detected in lesions of the distal esophagus, including 91% of Barrett's esophagus (n = 11), 100% of high-grade dysplasia (HGD, n = 5), and 81% of esophageal adenocarcinoma (EAC, n = 26) but absent in controls (n = 9). Vimentin methylation similarly was detected in 87% of signet ring (n = 15) and 53% of intestinal type gastric cancers (n = 17). Moreover, in tests of cytology brushings vimentin methylation proved detectable in 100% of Barrett's esophagus cases (n = 7), 100% of HGD cases (n = 4), and 83% of EAC cases (n = 18) but was absent in all controls (n = 5).

Conclusions: These findings establish aberrant vimentin methylation as a highly common epigenetic alteration in neoplasia of the upper gastrointestinal tract and show that Barrett's esophagus, even without dysplasia, already contains epigenetic alterations characteristic of adenocarcinoma.

Impact: These findings suggest vimentin methylation as a biomarker of upper gastrointestinal neoplasia with potential for development as molecular cytology in esophageal screening.

©2012 AACR.

PubMed Disclaimer

Figures

Figure 1

Figure 1

Vimentin methylation in Barrett’s Esophagus and esophageal neoplasias. Shown is percent of Vimentin methylation relative to total actin DNA detected in each sample. Circles denote individual samples. Samples in which no VIM methylation was detected are depicted as having 0.1% methylated DNA, which in most cases represented the lower limit of detection of the assay. In a few samples in which a lesser amount of input DNA was available, bars raised above the 0.1% level designate the slightly higher threshold that applied as the lower limit for detection of positive VIM methylation. Normal: Normal Squamous Mucosa; BE: Barrett’s Esophagus; HGD: High-Grade Dysplasia; EAC: Esophageal Adenocarcinoma; SCC: Squamous Cell Cancer of the Esophagus.

Figure 2

Figure 2

Percent Vimentin methylation in targeted esophageal brushings.from individuals with: BE: Barrett’s Esophagus; HGD: High Grade Dysplasia; EAC: Adenocarcinoma of the Esophagus, as well as from normal controls who were sampled in both squamous esophagus (SQ), and gastric cardia (cardia).

Figure 3

Figure 3

Vimentin methylation in gastric, small intestinal, pancreatic and duodenal cancer. Shown is percent of Vimentin methylation relative to total actin DNA in each sample. Circles denote individual samples. Samples in which no VIM methylation was detected are depicted as having 0.1% methylated DNA, which in most cases represented the lower limit of detection of the assay. In a few samples in which a lesser amount of input DNA was available, bars raised above the 0.1% level designate the slightly higher threshold that applied as the lower limit for detection of positive VIM methylation.. Panel A: Normal-1: Normal gastric mucosa from cancer free cases; Normal-2: Normal gastric mucosa from cases with concurrent gastric cancers; Signet Ring Cancer: Signet Ring Gastric Cancer samples; Intestinal Type Cancer: Intestinal Type Gastric Cancer samples. Panel B: Normal, morphologically normal duodenal tissue from patients with duodenal adenoma or cancer; Duodenal Cancer: Duodenal Cancer Samples; SI Cancer: Small Intestinal Cancer Samples; Pancreatic Cancer: Pancreatic Cancer Samples.

Comment in

References

    1. Kim MS, Lee J, Sidransky D. DNA methylation markers in colorectal cancer. Cancer Metastasis Rev. 2010 Mar;29(1):181–206. - PubMed
    1. Chen W-D, Han ZJ, Skoletsky J, Olson J, Sah J, Myeroff L, et al. Detection in fecal DNA of colon cancer-specific methylation of the nonexpressed vimentin gene. J. Natl. Cancer Inst. 2005 Aug 3;97(15):1124–1132. - PubMed
    1. Itzkowitz S, Brand R, Jandorf L, Durkee K, Millholland J, Rabeneck L, et al. A simplified, noninvasive stool DNA test for colorectal cancer detection. Am. J. Gastroenterol. 2008 Nov;103(11):2862–2870. - PubMed
    1. Li M, Chen W-D, Papadopoulos N, Goodman SN, Bjerregaard NC, Laurberg S, et al. Sensitive digital quantification of DNA methylation in clinical samples. Nat. Biotechnol. 2009 Sep;27(9):858–863. - PMC - PubMed
    1. Costa VL, Henrique R, Danielsen SA, Duarte-Pereira S, Eknaes M, Skotheim RI, et al. Three epigenetic biomarkers, GDF15, TMEFF2, and VIM, accurately predict bladder cancer from DNA-based analyses of urine samples. Clin. Cancer Res. 2010 Dec 1;16(23):5842–5851. - PubMed

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources