Detection of BRAFV600E mutation on fine needle aspiration specimens of thyroid nodule refines cyto-pathology diagnosis, especially in BRAFV600E mutation-prevalent area.

Background Between 10 and 30% of the fine needle aspiration biopsies (FNABs) of thyroid nodules are diagnosed as ‘indeterminate’. A molecular diagnostic method is needed to reduce unnecessary surgery in this group. In Korea, most thyroid cancer is the classic papillary type and the BRAFV600E mutation is highly prevalent. Aim To evaluate the role of pre-operative detection of BRAFV600E mutation in the FNAB specimens of thyroid nodules in a BRAFV600E mutation-prevalent geographical area. Patients and methods In 137 specimens of FNAB (107 papillary thyroid carcinomas (PTC); 3 follicular thyroid carcinomas (FTC); 2 undifferentiated thyroid carcinomas; 25 benign lesions), both direct DNA sequencing and PCR-RFLP were used for detecting the BRAFV600E mutation. The sensitivity and specificity were calculated. We analysed the association between BRAFV600E mutation and the clinico-pathological parameters. Results The BRAFV600E mutation was present in 93 (83%) of 112 thyroid cancers. Direct DNA sequencing showed a sensitivity of 83·0% and a specificity of 96·0%. The sensitivity and specificity of PCR-RFLP were 78·6% and 80·0%, respectively. Among 25 cases with indeterminate FNAB cytology, 8 patients had malignant lesions (5 PTC and 3 FTC). Three (60%) of 5 PTCs and 1 out of 17 benign lesions had BRAFV600E mutation (only one false positive case and the definitive pathology showed atypical nodular hyperplasia that could be a premalignant lesion). The diagnostic accuracy of this molecular method in only the 25 indeterminate nodules was 76% (19/25). No mutation was found in 3 FTCs. Among 107 PTCs, there was no significant association of the BRAFV600E mutation with the known risk factors. Conclusion Detection of the BRAFV600E mutation in FNAB specimens refines the FNAB-cytology diagnosis, especially in a BRAFV600E mutation-prevalent area. Direct DNA sequencing was a more reliable method than PCR-RFLP for detecting the BRAFV600E mutation with a high sensitivity and specificity. [ABSTRACT FROM AUTHOR]