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DNA methylation analysis for the diagnosis of thyroid nodules – a pilot study with reference to BRAF V 600E mutation and cytopathology results
Author(s) -
Chang H.,
Shin B. K.,
Kim A.,
Kim H. K.,
Kim B. H.
Publication year - 2016
Publication title -
cytopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.512
H-Index - 48
eISSN - 1365-2303
pISSN - 0956-5507
DOI - 10.1111/cyt.12248
Subject(s) - cytopathology , thyroid nodules , medicine , methylation , fine needle aspiration , dna methylation , pathology , thyroid carcinoma , thyroid , carcinogenesis , cancer research , cancer , cytology , gene , biology , biopsy , gene expression , genetics
Objective Promoter hypermethylation and the BRAF V 600E 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 BRAF V 600E 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 BRAF V 600E mutation status of the FNA samples. Results We identified five genes that were significantly hypermethylated in malignant tissues: PTGS 2 , HOXA 1 , TMEFF 2 , p16 and PTEN . With respect to diagnostic potential, results obtained using the BRAF V 600E 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 .