Aberrant vimentin methylation is characteristic of upper gastrointestinal pathologies.
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.


CONCLUSIONS
These findings suggest vimentin methylation as a biomarker of upper gastrointestinal neoplasia with potential for development as molecular cytology in esophageal screening.
Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, USA.
Helen
H
Moinova
Rom S
RS
Leidner
Lakshmeswari
L
Ravi
James
J
Lutterbaugh
Jill S
JS
Barnholtz-Sloan
Yanwen
Y
Chen
Amitabh
A
Chak
Sanford D
SD
Markowitz
Joseph E
JE
Willis
D000230:Adenocarcinoma / Q000235:genetics; D001471:Barrett Esophagus / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000235:genetics*; D016022:Case-Control Studies; D004247:DNA / Q000235:genetics; D019175:DNA Methylation; D018450:Disease Progression; D005500:Follow-Up Studies; D005770:Gastrointestinal Neoplasms / Q000235:genetics*; D006801:Humans; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D014746:Vimentin / Q000235:genetics*
D014408:Biomarkers, Tumor; D014746:Vimentin; D004247:DNA