Detection of RET/PTC, TRK and BRAF mutations in preoperative diagnosis of thyroid nodules with indeterminate cytological findings.
BACKGROUND
Fine-needle aspiration biopsy (FNAB) is the primary means to distinguish benign from malignant nodules and select patients for surgery. However, adjunctive diagnostic tests are needed because in 20-40% of cases the FNAB result is uncertain.


OBJECTIVE
We investigated whether a search for the oncogenes RET/PTC, TRK and BRAF(V600E) in thyroid aspirates could refine an uncertain diagnosis.


METHODS
A total of 132 thyroid aspirates, including colloid nodules, inadequate samplings, indeterminate and suspicious for malignancy were analysed by reverse transcription polymerase chain reaction (RT-PCR) and mutant allele-specific amplification techniques for the presence of oncogenes.


RESULTS
No oncogenes were detected in 48 colloid nodules, 46 inadequate and 19 indeterminate FNABs, then confirmed to be benign at histology. No oncogenes were detected in one follicular thyroid cancer (FTC) with indeterminate cytology. Five out of six papillary thyroid cancers (83%) with FNAB suspicious for malignancy were correctly diagnosed by the presence of oncogenes. Among these, four (67%) contained the BRAF mutation and one (17%) contained RET/PTC-3. On final analysis, no false-positive results were reported in 131 samples and five out of seven carcinomas (71%) were correctly diagnosed. The finding of oncogenes in FNAB specimens suspicious for malignancy guided the extent of surgical resection, changing the surgery from diagnostic to therapeutic in five cases.


CONCLUSIONS
Detection of RET/PTC, TRK and BRAF(V600E) in FNAB specimens is proposed as a diagnostic adjunctive tool in the evaluation of thyroid nodules with suspicious cytological findings.
Sapio
Maria Rosaria
MR
Department of Endocrinologia ed Oncologia Molecolare e Clinica, Università Federico II, Naples, Italy.
Posca
Daniela
D
Raggioli
Angelo
A
Guerra
Anna
A
Marotta
Vincenzo
V
Deandrea
Maurilio
M
Motta
Manuela
M
Limone
Paolo Piero
PP
Troncone
Giancarlo
G
Caleo
Alessia
A
Rossi
Guido
G
Fenzi
Gianfranco
G
Vitale
Mario
M
D001707:Biopsy, Needle; D002291:Carcinoma, Papillary / Q000235:genetics* / Q000473:pathology; D018265:Carcinoma, Papillary, Follicular / Q000235:genetics; D004252:DNA Mutational Analysis; D003937:Diagnosis, Differential; D015321:Gene Rearrangement; D006801:Humans; D009857:Oncogenes; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology; D016606:Thyroid Nodule / Q000235:genetics* / Q000473:pathology
D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf