Abstract
BackgroundEsophageal cancer is the sixth leading cause of cancer death worldwide; current early detection screening tests are inadequate. Esophageal balloon cytology successfully retrieves exfoliated and scraped superficial esophageal epithelial cells, but cytologic reading of these cells has poor sensitivity and specificity for detecting esophageal squamous dysplasia (ESD), the precursor lesion of esophageal squamous cell carcinoma (ESCC). Measuring telomere length, a marker for chromosomal instability, may improve the utility of balloon cytology for detecting ESD and early ESCC.MethodsWe examined balloon cytology specimens from 89 asymptomatic cases of ESD (37 low-grade and 52 high-grade) and 92 age- and sex-matched normal controls from an esophageal cancer early detection screening study. All subjects also underwent endoscopy and biopsy, and ESD was diagnosed histopathologically. DNA was extracted from the balloon cytology cells, and telomere length was measured by quantitative PCR. A receiver operating characteristic (ROC) curve was plotted for telomere length as a diagnostic marker for high-grade dysplasia.ResultsTelomere lengths were comparable among the low- and high-grade dysplasia cases and controls, with means of 0.96, 0.96, and 0.92, respectively. The area under the ROC curve was 0.55 for telomere length as a diagnostic marker for high-grade dysplasia. Further adjustment for subject characteristics, including sex, age, smoking, drinking, hypertension, and body mass index did not improve the use of telomere length as a marker for ESD.ConclusionsTelomere length of esophageal balloon cytology cells was not associated with ESCC precursor lesions. Therefore, telomere length shows little promise as an early detection marker for ESCC in esophageal balloon samples.
Highlights
Esophageal cancer is the sixth leading cause of cancer death worldwide; current early detection screening tests are inadequate
A validated early detection marker for esophageal squamous dysplasia (ESD) might eventually serve as a target for the future development of inexpensive and rapid point-of-care molecular diagnostics that could be used to augment balloon cytology in resource-limited locations
Given the evidence that esophageal squamous cell carcinoma (ESCC) tumor cells may have shortened telomeres and given that non-malignant esophageal epithelial cells from cancer patients have shorter telomeres compared with normal esophageal cells from non-cancer patients [29], we aimed to examine the telomere length of DNA extracted from balloon cytology-collected esophageal cells as a potential early detection biomarker for ESD, the histologic precursor of ESCC
Summary
Esophageal cancer is the sixth leading cause of cancer death worldwide; current early detection screening tests are inadequate. Endoscopy is time-consuming, invasive, and requires specially trained personnel and equipment to perform the examination, take biopsies, and make appropriate pathologic diagnoses, so frequent endoscopy for ESCC early detection screening in highrisk asymptomatic populations in underdeveloped settings with inadequate health resources remains a major challenge [12]. A simple and inexpensive method of retrieving esophageal cells, has been commonly used in China for diagnosing patients with dysphagia or for screening asymptomatic, high-risk populations for esophageal cancer [13]. If a biomarker of esophageal disease that could be measured in the balloon cytology cells could improve the sensitivity and specificity of this cell collection technique for detecting ESD, it might make an important public health impact. A validated early detection marker for ESD might eventually serve as a target for the future development of inexpensive and rapid point-of-care molecular diagnostics that could be used to augment balloon cytology in resource-limited locations
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