Detection of BRAFV600E mutation on fine needle aspiration specimens of thyroid nodule refines cyto-pathology diagnosis, especially in BRAF600E 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 BRAF(V600E) mutation is highly prevalent.


OBJECTIVE
To evaluate the role of pre-operative detection of BRAF(V600E) mutation in the FNAB specimens of thyroid nodules in a BRAF(V600E) mutation-prevalent geographical area.


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 BRAF(V600E) mutation. The sensitivity and specificity were calculated. We analysed the association between BRAF(V600E) mutation and the clinico-pathological parameters.


RESULTS
The BRAF(V600E) 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 BRAF(V600E) 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 BRAF(V600E) mutation with the known risk factors.


CONCLUSIONS
Detection of the BRAF(V600E) mutation in FNAB specimens refines the FNAB-cytology diagnosis, especially in a BRAF(V600E) mutation-prevalent area. Direct DNA sequencing was a more reliable method than PCR-RFLP for detecting the BRAF(V600E) mutation with a high sensitivity and specificity.
Chung
Ki-wook
KW
Research Institute and Hospital, National Cancer Centre, Goyang, Gyeonggi, Korea.
Yang
Sun Kyung
SK
Lee
Geon Kook
GK
Kim
Eun Young
EY
Kwon
Soim
S
Lee
Sang Hyun
SH
Park
Do Joon
DJ
Lee
Hyun Sook
HS
Cho
Bo Youn
BY
Lee
Eun Sook
ES
Kim
Sun Wook
SW
D018263:Adenocarcinoma, Follicular / Q000235:genetics; D000328:Adult; D000368:Aged; D044963:Biopsy, Fine-Needle; D002291:Carcinoma, Papillary / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D018265:Carcinoma, Papillary, Follicular / Q000235:genetics; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000032:analysis; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D007723:Korea; D008297:Male; D008875:Middle Aged; D017354:Point Mutation; D012150:Polymorphism, Restriction Fragment Length; D011446:Prospective Studies; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D012680:Sensitivity and Specificity; D013964:Thyroid Neoplasms / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D016606:Thyroid Nodule / Q000208:ethnology / Q000235:genetics* / Q000473:pathology
D004273:DNA, Neoplasm; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf