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. 2008 Oct;1(5):357-61.
doi: 10.1158/1940-6207.CAPR-08-0061.

Promoter methylation in cytology specimens as an early detection marker for esophageal squamous dysplasia and early esophageal squamous cell carcinoma

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Promoter methylation in cytology specimens as an early detection marker for esophageal squamous dysplasia and early esophageal squamous cell carcinoma

Lisa Adams et al. Cancer Prev Res (Phila). 2008 Oct.

Abstract

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 biopsyproven 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.

Keywords: cytology; early detection; esophageal squamous cell cancer; gene methylation.

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Figures

Figure 1
Figure 1
Proportion of patients with various numbers of methylated genes, according to patients’ pathological category. The average number of methylated genes (from Table 2) are 0.50, 0.92, 0.72, 0.96, and 1.29 for the Normal, Esophagitis, Mild, Moderate, and Severe Dysplasia histologic categories, respectively. Test for the trend of 3+ genes methylated across the histologic spectrum from normal through severe dysplasia: ptrend=0.02 (chi-square test).

References

    1. Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55:74–108. - PubMed
    1. Edwards BK, Brown ML, Wingo PA, et al. Annual report to the nation on the status of cancer, 1975–2002, featuring population-based trends in cancer treatment. J Natl Cancer Inst. 2005;97:1407–1427. - PubMed
    1. Wang GQ, Abnet CC, Shen Q, et al. Histological precursors of oesophageal squamous cell carcinoma: results from a 13 year prospective follow up study in a high risk population. Gut. 2005;54:187–192. - PMC - PubMed
    1. Tachibana M, Hirahara N, Kinugasa S, Yoshimura H. Clinicopathologic features of superficial esophageal cancer: results of consecutive 100 patients. Ann Surg Oncol. 2008;15:104–116. - PubMed
    1. Dawsey SM, Shen Q, Nieberg RK, et al. Studies of esophageal balloon cytology in Linxian, China. Cancer Epidemiol Biomarkers Prev. 1997;6:121–130. - PubMed

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