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ORIGINAL ARTICLE
Year : 2018  |  Volume : 22  |  Issue : 3  |  Page : 339-346

Molecular profiling of follicular variant of papillary thyroid cancer reveals low-risk noninvasive follicular thyroid neoplasm with papillary-like nuclear features: A paradigm shift to reduce aggressive treatment of indolent tumors


1 Department of Endocrine Surgery, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
2 Department of Pathology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
3 Department of Medical Genetics, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
4 Department of Endocrinology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India

Correspondence Address:
Amit Agarwal
Department of Endocrine Surgery, SGPGIMS, Lucknow, Uttar Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijem.IJEM_86_18

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Introduction: Encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC) has been reclassified into noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) and invasive EFVPTC. NIFTP is considered a low-risk neoplasm. Therefore, follicular variant of papillary thyroid cancer (FVPTC) presently has two distinct histopathological subtypes – invasive EFVPTC and infiltrative/diffuse FVPTC. Molecular characteristics of these groups remain unclear. Methodology: Thirty FVPTCs (10 NIFTPs, 12 invasive EFVPTCs, and 8 infiltrative/diffuse variants) were reviewed and screened for BRAF and RAS mutations by restriction fragment length morphism-polymerase chain reaction (PCR) and Sanger sequencing. The mRNA expression levels of iodine-metabolizing genes were analyzed using real-time PCR. The mutations status and mRNA expression levels were correlated with clinicopathological features. Results: All 10 NIFTPs had predominant follicular pattern. One case showed NRAS mutation, whereas none showed BRAF mutation. All invasive EFVPTC had capsular and/or lymphovascular invasion and 4/12 showed lymph node metastasis. BRAF and NRAS were seen in three cases each of invasive FVPTC. All eight infiltrating/diffuse FVPTCs showed infiltration into adjacent thyroid parenchyma and lymph node metastasis. Conclusion: BRAF mutation was observed in 62.5% of cases; however, no NRAS mutation was found. Sodium iodide symporter (NIS) expressions in NIFTP were similar to that of normal thyroid tissue, whereas it was downregulated in invasive and infiltrative/diffuse FVPTC. Our study supports the argument that NIFTP can be considered as low-risk follicular thyroid neoplasm. Those tumors that harbor BRAF mutations may be offered a complete thyroidectomy because they show decreased expression of NIS gene which confers a tendency to lose radioactive iodine avidity and further recurrence of the tumor.


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