DIAGNOSTIC AND PROGNOSTIC UTILITY OF NRAS MUTATION GENE TESTING IN CYTOLOGICALLY INDETERMINATE THYROID NODULES

Objective: to evaluate the diagnostic and prognostic impact of NRAS mutational gene testing in fine needle aspiration samples from cytologically indeterminate thyroid nodules. Background: Fine needle aspiration cytology (F.N.A.C) is the cornererstone of assessment of thyroid nodules, but 15 to 30% of aspirates are indeterminate and are mostly referred for diagnostic surgery; exposing patients to postoperative undue effects. This raises the need to improve preoperative diagnosis of such nodules and here's the role of molecular markers (like RAS) detection in aspirates from these nodules as an adjunct to F.N.A.C. Patients and Methods: In this study 100 patients with cytologically indeterminate thyroid nodules were subjected to NRAS gene mutation testing at exons 12/13 & 61 by direct sequencing. 90 cases were managed surgically, while 10 cases were followed up by ultrasound (U.S) after 1 year. Results: The incidence of NRAS mutation was 34%, of which NRAS exon 61 mutations were the commonest (76.4%). In surgery correlation group, 19.6% of the benign cases were +ve for NRAS mutation (all were F.As), while of the malignant cases, 61.5% were +ve for NRAS mutation. The probability of cancer in NRAS +ve cases was 70.6%. The PPV, NPV, sensitivity and specificity for NRAS mutation testing was 70.6%, 73.2%, 61.5% and 80.4% respectively. The accuracy of NRAS mutation testing was 72.2%. Conclusion: NRAS gene mutational testing represents a promising diagnostic tool for patients with cytologically indeterminate thyroid nodules especially those with follicular patterned thyroid lesions (F.A, F.V.P.T.C &F.T.C) and can be used as a tumor marker in such patients.