A morpho-molecular diagnosis of papillary thyroid carcinoma: BRAF V600E detection as an important tool in preoperative evaluation of fine-needle aspirates.
BACKGROUND
Although most thyroid nodule fine-needle aspiration (FNA) diagnoses are definitive or nearly definitive, about 30% of them are not read as definitively benign or malignant, the so-called indeterminate or suspicious FNA diagnosis. The prevalence of malignancy in FNA samples with these diagnoses varies from 10% to 52%. The first aim of this study was to determine if BRAF V600E analysis of thyroid FNA cytological smears could be performed with a relatively simple protocol. We also sought to determine if assessing the presence of BRAF gene mutations in preoperative FNA cytology slides would provide diagnostic information for FNA samples with a reading of indeterminate or suspicious thyroid lesions.


METHODS
DNA was extracted directly from FNA-stained smears of 111 patients with thyroid lesions having different cytological diagnoses. There was 1 cystic nodule, 20 microfollicular proliferations without atypia, 32 that were suspicious for papillary carcinoma, 56 papillary thyroid carcinomas (PTC), and 2 poorly differentiated carcinomas. The BRAF V600E mutational status was determined by sequencing analysis in all patients. The histopathological diagnosis was obtained in all cases.


RESULTS
We observed that 56/90 (62.3%) patients received a definitive diagnosis of PTC when only cytology was used. After molecular analysis, the BRAF V600E mutation was detected in 18/32 (56.2%) cases with a cytology of suspicious for papillary carcinoma and 41/56 (73.2%) with PTC. According to the morpho-molecular analysis (i.e., traditional cytology combined with BRAF V600E analysis) 74/90 (82.2%) patients could be assigned a definitive diagnosis of PTC. Therefore, the addition of molecular analysis yielded an increase of 20% in the sensitivity compared to cytology alone.


CONCLUSIONS
The method of molecular analysis of thyroid FNA smears described here can be easily performed after the FNA, thereby avoiding inconvenience and additional time during the FNA and permitting later analysis of samples having indeterminate cytology features. The increased sensitivity of this preoperative morpho-molecular analysis should provide information that is useful in deciding the extent of thyroid surgery for thyroid nodules that are indeterminate or suspicious on cytology.
Marchetti
Ivo
I
University of Pisa and Pisa University Hospital, Italy. i.marchetti@ao-pisa.toscana.it
Lessi
Francesca
F
Mazzanti
Chiara Maria
CM
Bertacca
Gloria
G
Elisei
Rossella
R
Coscio
Giancarlo Di
GD
Pinchera
Aldo
A
Bevilacqua
Generoso
G
D000293:Adolescent; D000328:Adult; D000368:Aged; D044963:Biopsy, Fine-Needle / Q000379:methods*; D018265:Carcinoma, Papillary, Follicular / Q000175:diagnosis* / Q000235:genetics* / Q000378:metabolism; D002648:Child; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D008297:Male; D008495:Medical Oncology; D008875:Middle Aged; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D013961:Thyroid Gland / Q000473:pathology; D013964:Thyroid Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000378:metabolism
C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf