Cancer Prevention Research 1, 357-361, October 1, 2008. doi: 10.1158/1940-6207.CAPR-08-0061
© 2008 American Association for Cancer Research
Promoter Methylation in Cytology Specimens as an Early Detection Marker for Esophageal Squamous Dysplasia and Early Esophageal Squamous Cell Carcinoma
Lisa Adams1,
Mark J. Roth2,
Christian C. Abnet2,
Sonja P. Dawsey1,
You-Lin Qiao3,
Guo-Qing Wang4,
Wen-Qiang Wei3,
Ning Lu5,
Sanford M. Dawsey2 and
Karen Woodson1
Authors' Affiliations: 1 Genetics Branch, Center for Cancer Research and 2 Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland; 3 Department of Cancer Epidemiology, 4 Department of Endoscopy, and 5 Department of Pathology, Cancer Institute, Chinese Academy of Medical Sciences, Beijing, China
Requests for reprints: Mark J. Roth, Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, 6120 Executive Boulevard, EPS/320 MSC 7232, Rockville, MD 20852. Phone: 301-402-8276; Fax: 301-435-8645; E-mail: mr166i{at}nih.gov.
The incidence of esophageal squamous cell carcinoma (ESCC) is very high in northern China. This cancer has a very poor prognosis, mostly because it is usually diagnosed at a late stage. Detection at an earlier stage can dramatically improve prognosis. Microscopic evaluation of esophageal balloon cytology (EBC) specimens has been the most common method for early detection of ESCC, but this technique is limited by low sensitivity and specificity. The use of molecular markers may improve these screening characteristics. This study evaluates whether measurement of gene methylation in EBC specimens may have utility for the detection of esophageal squamous dysplasia and early ESCC. We evaluated the presence of methylation in eight genes shown to be methylated in ESCC in previous studies in EBC specimens from 147 patients with endoscopic biopsy diagnoses ranging from normal mucosa to severe squamous dysplasia. Methylation status was determined using quantitative methylation-specific PCR techniques. The sensitivity and specificity of methylation of each individual gene and of combinations of these genes to detect biopsy-proven high-grade (moderate or severe) squamous dysplasia were determined. For individual genes, the sensitivities ranged from 9% to 34% and the specificities ranged from 77% to 99%. Using a panel of four genes (AHRR, p16INK4a, MT1G, and CLDN3) resulted in sensitivity and specificity of 50% and 68%, respectively. This study suggests that evaluation of gene methylation in EBC samples may have utility for early detection of esophageal squamous dysplasia and early ESCC; however, identification of more sensitive methylation markers will be required for development of a clinically useful screening test.
Key Words: gene methylation • early detection • cytology • esophageal squamous cell cancer
Copyright © 2008 by the American Association for Cancer Research.
