Highly Sensitive and Specific Molecular Test for Mutations in the Diagnosis of Thyroid Nodules: A Prospective Study of BRAF-Prevalent Population.

Molecular testing offers more objective information in the diagnosis and personalized decision making for thyroid nodules. In Korea, as the BRAF V600E mutation is detected in 70-80% of thyroid cancer specimens, its testing in fine-needle aspiration (FNA) cytology specimens alone has been used for the differential diagnosis of thyroid nodules until now. Thus, we aimed to develop a mutation panel to detect not only BRAF V600E, but also other common genetic alterations in thyroid cancer and to evaluate the diagnostic accuracy of the mutation panel for thyroid nodules in Korea. For this prospective study, FNA specimens of 430 nodules were obtained from patients who underwent thyroid surgery for thyroid nodules. A molecular test was devised using real-time PCR to detect common genetic alterations in thyroid cancer, including BRAF, N-, H-, and K-RAS mutations and rearrangements of RET/PTC and PAX8/PPARr. Positive results for the mutation panel were confirmed by sequencing. Among the 430 FNA specimens, genetic alterations were detected in 293 cases (68%). BRAF V600E (240 of 347 cases, 69%) was the most prevalent mutation in thyroid cancer. The RAS mutation was most prevalently detected for indeterminate cytology. Among the 293 mutation-positive cases, 287 (98%) were diagnosed as cancer. The combination of molecular testing and cytology improved sensitivity from 72% (cytology alone) to 89% (combination), with a specificity of 93%. We verified the excellent diagnostic performance of the mutation panel applicable for clinical practice in Korea. A plan has been devised to validate its performance using independent FNA specimens.

Molecular genotyping of the non-invasive encapsulated follicular variant of papillary thyroid carcinoma.

AIMS: The non-invasive encapsulated follicular variant of papillary thyroid carcinoma (FVPTC) has been managed as a low-risk malignancy. Recently, a proposal was made to reclassify this tumour type as a premalignant lesion and rename it non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). This study aims to provide the first comprehensive study on molecular genotype-phenotype correlations of encapsulated FVPTC. METHODS AND RESULTS: This study was performed on 177 consecutive FVPTCs from January 2014 to April 2016. These were classified as non-invasive encapsulated FVPTC (n = 74) invasive encapsulated FVPTC (n = 51), and infiltrative FVPTC (n = 52), according to standard criteria, by two independent pathologists. Genetic alterations and other clinicopathological information were compared. BRAFV600E was found in 12.2% (non-invasive) and 11.8% (invasive) of encapsulated FVPTCs, and in 34.6% of infiltrative FVPTCs (P = 0.001). Mutation in encapsulated FVPTCs was limited to cases with rare or abortive papillae. RET-PTC1 and RET-PTC3 rearrangements were present (11.5%) only in infiltrative FVPTCs. In contrast, NRAS, HRAS and KRAS mutations were observed more often in encapsulated FVPTCs (48.6% in non-invasive and 66.7% in invasive) than in infiltrative FVPTCs (15.4%) (P < 0.001). Preoperative cytological examination did not distinguish between non-invasive and invasive encapsulated FVPTCs, whereas infiltrative FVPTC was more likely to be Bethesda class V/VI than the encapsulated type (60.4% versus 38.1%; P = 0.01). CONCLUSIONS: There were no differences in clinicopathological or molecular profiles between non-invasive and invasive encapsulated FVPTCs, except in vascular and capsular invasion. Therefore, the diagnosis of NIFTP, like that of follicular adenoma, may require surgical resection and exclusion of those tumours with any papillae.