DNA methylation analysis for the diagnosis of thyroid nodules - a pilot study with reference to BRAFV 600E mutation and cytopathology results

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2 Citations (Scopus)

Abstract

Objective: Promoter hypermethylation and the BRAFV600E mutation are both involved in thyroid tumorigenesis. We conducted a pilot study on the diagnosis of thyroid nodules by analysis of promoter hypermethylation status with reference to BRAFV600E mutation and cytopathology results using formalin-fixed, paraffin-embedded (FFPE) tissues and liquid-based preparation (LBP) thyroid fine needle aspiration (FNA) samples to predict more reliably the possibility of papillary carcinoma. Methods: We initially performed MethyLight analysis for 30 genes that are known to be hypermethylated in malignancies using 164 papillary carcinomas and 77 benign tissue samples. Five genes selected from the tissue analysis were subsequently analysed in 75 surgically proven benign and 66 surgically proven papillary carcinoma LBP FNA samples. Samples that showed two or more positive results among the five genes were classified as methylation positive. We also analysed the BRAFV600E mutation status of the FNA samples. Results: We identified five genes that were significantly hypermethylated in malignant tissues: PTGS2, HOXA1, TMEFF2, p16 and PTEN. With respect to diagnostic potential, results obtained using the BRAFV600E mutation test combined with cytological examination were not significantly different from those obtained with cytological examination only. Combining methylation analyses with cytological examination or performing all three tests for diagnoses did not improve significantly the negative predictive values and sensitivity, but a significant decrease in positive predictive value and specificity was observed. Conclusion: Further studies are needed on larger samples to assess the potential value of methylation analysis of thyroid FNA.

Original languageEnglish
Pages (from-to)122-130
Number of pages9
JournalCytopathology
Volume27
Issue number2
DOIs
Publication statusPublished - 2016 Apr 1

Keywords

  • BRAF
  • Liquid-based preparation
  • Methylation
  • Papillary carcinoma
  • Thyroid

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology

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