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 RARbeta2) 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.
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 RARbeta2) on 96 bisulfite-treated serum DNA samples isolated preoperatively from either solid thyroid nodulepatients 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 cancerpatients. 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.
Authors: Mariana Brait; Myriam Loyo; Eli Rosenbaum; Kimberly L Ostrow; Alina Markova; Silvana Papagerakis; Marianna Zahurak; Steven M Goodman; Martha Zeiger; David Sidransky; Christopher B Umbricht; Mohammad O Hoque Journal: Epigenetics Date: 2012-07-01 Impact factor: 4.528
Authors: Semra Demokan; Xiaofei Chang; Alice Chuang; Wojciech K Mydlarz; Jatinder Kaur; Peng Huang; Zubair Khan; Tanbir Khan; Kimberly L Ostrow; Mariana Brait; Mohammad O Hoque; Nanette J Liegeois; David Sidransky; Wayne Koch; Joseph A Califano Journal: Int J Cancer Date: 2010-11-15 Impact factor: 7.396