Impact of proto-oncogene mutation detection in cytological specimens from thyroid nodules improves the diagnostic accuracy of cytology.
BACKGROUND
Fine-needle aspiration cytology (FNAC) is the gold standard for the differential diagnosis of thyroid nodules but has the limitation of inadequate sampling or indeterminate lesions.


OBJECTIVE
We aimed to verify whether search of thyroid cancer-associated protooncogene mutations in cytological samples may improve the diagnostic accuracy of FNAC.


METHODS
One hundred seventy-four consecutive patients undergoing thyroid surgery were submitted to FNAC (on 235 thyroid nodules) that was used for cytology and molecular analysis of BRAF, RAS, RET, TRK, and PPRgamma mutations. At surgery these nodules were sampled to perform the same molecular testing.


RESULTS
Mutations were found in 67 of 235 (28.5%) cytological samples. Of the 67 mutated samples, 23 (34.3%) were mutated by RAS, 33 (49.3%) by BRAF, and 11 (16.4%) by RET/PTC. In 88.2% of the cases, the mutation was confirmed in tissue sample. The presence of mutations at cytology was associated with cancer 91.1% of the times and follicular adenoma 8.9% of the time. BRAF or RET/PTC mutations were always associated with cancer, whereas RAS mutations were mainly associated with cancer (74%) but also follicular adenoma (26%). The diagnostic performance of molecular analysis was superior to that of traditional cytology, with better sensitivity and specificity, and the combination of the two techniques further contributed to improve the total accuracy (93.2%), compared with molecular analysis (90.2%) or traditional cytology (83.0%).


CONCLUSIONS
Our findings demonstrate that molecular analysis of cytological specimens is feasible and that its results in combination with cytology improves the diagnostic performance of traditional cytology.
Section of Endocrinology and Metabolism, Department of Internal Medicine, Endocrinology, and Metabolism and Biochemistry, University of Siena, Policlinico Santa Maria alle Scotte, Viale Bracci 1, 53100 Siena, Italy.
Silvia
S
Cantara
Marco
M
Capezzone
Stefania
S
Marchisotta
Serena
S
Capuano
Giulia
G
Busonero
Paolo
P
Toti
Andrea
A
Di Santo
Giuseppe
G
Caruso
Anton Ferdinando
AF
Carli
Lucia
L
Brilli
Annalisa
A
Montanaro
Furio
F
Pacini
D000236:Adenoma / Q000175:diagnosis* / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics; D044963:Biopsy, Fine-Needle; D002291:Carcinoma, Papillary / Q000175:diagnosis* / Q000235:genetics; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013964:Thyroid Neoplasms / Q000175:diagnosis* / Q000235:genetics; D016606:Thyroid Nodule / Q000175:diagnosis* / Q000235:genetics
D014408:Biomarkers, Tumor; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins