TY - JOUR
T1 - Detection of serum deoxyribonucleic acid methylation markers
T2 - A novel diagnostic tool for thyroid cancer
AU - Hu, Shuiying
AU - Ewertz, Marjorie
AU - Tufano, Ralph P.
AU - Brait, Mariana
AU - Carvalho, Andre Lopes
AU - Liu, Dingxie
AU - Tufaro, Anthony P.
AU - Basaria, Shehzad
AU - Cooper, David S.
AU - Sidransky, David
AU - Ladenson, Paul W.
AU - Xing, Mingzhao
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2006/1
Y1 - 2006/1
N2 - Context: Serum DNA methylation markers may potentially be useful in diagnosing thyroid cancer and monitoring its recurrence. Objective: The objective of the study was to assess the utility of serum DNA methylation as a diagnostic test for patients with thyroid nodules and a monitoring test to detect thyroid cancer recurrence in previously treated patients. Design, Setting, and Subjects: Using real-time quantitative methylation-specific PCR, we analyzed the methylation status of five genes (CALCA, CDH1, TIMP3, DAPK, and RARβ2) on 96 bisulfite-treated serum DNA samples isolated preoperatively from either solid thyroid nodule patients or patients in follow-up for history of treated thyroid cancer. Main Outcome Measure: Diagnostic sensitivity, specificity, and accuracy of serum DNA methylation marker for thyroid cancer were measured. Results: For the patients with thyroid nodules, when a positive result was defined by a serum methylation level above the appropriately chosen cutoff value for any one of the five genes, the preoperative diagnostic sensitivity for thyroid cancer was 68% (26 of 38), the specificity was 95% (18 of 19), and the overall preoperative diagnostic accuracy was 77%, with positive and negative predictive values of 96 and 60%, respectively. In a subset of patients with cytologically indeterminate thyroid nodules, serum DNA methylation testing could correctly diagnose eight of 11 (73%) cancers and four of four (100%) benign tumors, with a diagnostic accuracy of 80%. We also analyzed these serum DNA methylation markers in 39 previously treated thyroid cancer patients. Among the 10 patients proved to have recurrent disease by conventional measures, seven (70%) were positive on methylation testing. Among the 29 patients who had no corroboration of residual or recurrent disease by conventional studies, six (21%) were positive for serum DNA methylation markers. Conclusions: We have demonstrated the potential usefulness of serum DNA methylation markers as a novel tool for differential diagnosis of solid thyroid nodules and thyroid cancer recurrence monitoring.
AB - Context: Serum DNA methylation markers may potentially be useful in diagnosing thyroid cancer and monitoring its recurrence. Objective: The objective of the study was to assess the utility of serum DNA methylation as a diagnostic test for patients with thyroid nodules and a monitoring test to detect thyroid cancer recurrence in previously treated patients. Design, Setting, and Subjects: Using real-time quantitative methylation-specific PCR, we analyzed the methylation status of five genes (CALCA, CDH1, TIMP3, DAPK, and RARβ2) on 96 bisulfite-treated serum DNA samples isolated preoperatively from either solid thyroid nodule patients or patients in follow-up for history of treated thyroid cancer. Main Outcome Measure: Diagnostic sensitivity, specificity, and accuracy of serum DNA methylation marker for thyroid cancer were measured. Results: For the patients with thyroid nodules, when a positive result was defined by a serum methylation level above the appropriately chosen cutoff value for any one of the five genes, the preoperative diagnostic sensitivity for thyroid cancer was 68% (26 of 38), the specificity was 95% (18 of 19), and the overall preoperative diagnostic accuracy was 77%, with positive and negative predictive values of 96 and 60%, respectively. In a subset of patients with cytologically indeterminate thyroid nodules, serum DNA methylation testing could correctly diagnose eight of 11 (73%) cancers and four of four (100%) benign tumors, with a diagnostic accuracy of 80%. We also analyzed these serum DNA methylation markers in 39 previously treated thyroid cancer patients. Among the 10 patients proved to have recurrent disease by conventional measures, seven (70%) were positive on methylation testing. Among the 29 patients who had no corroboration of residual or recurrent disease by conventional studies, six (21%) were positive for serum DNA methylation markers. Conclusions: We have demonstrated the potential usefulness of serum DNA methylation markers as a novel tool for differential diagnosis of solid thyroid nodules and thyroid cancer recurrence monitoring.
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U2 - 10.1210/jc.2005-1810
DO - 10.1210/jc.2005-1810
M3 - Article
C2 - 16263813
AN - SCOPUS:30344472109
SN - 0021-972X
VL - 91
SP - 98
EP - 104
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 1
ER -