Impact of NRAS Q61R Mutations on Papillary Thyroid Carcinoma: A Correlation with Clinicopathological Parameters

Background: RAS gene mutations are found in a variety of malignancies throughout the body. NRAS mutations have been identified in several types of thyroid cancer. Although concurrent RAS mutations have recently been reported in papillary thyroid carcinoma (PTC), their impact on tumor progression and patient survival remains unclear. Objective: To investigate the significance of NRAS mutations in PTC and their correlation with clinicopathological characteristics. Materials and methods: Formalin-fixed paraffin-embedded tissue blocks were obtained from 60 histologically confirmed PTC cases, referred between June 2022 and June 2023 to the National Center for Education Laboratories, Medical City Campus, and AL-Kimma Private Hospital in Baghdad, Iraq. The study investigated the presence of the NRAS Q61R mutation in these samples and analyzed its association with various clinical and pathological parameters, including age, sex, PTC variants, tumor size, capsular invasion, multifocality, extrathyroidal extension, and lymph node metastasis. Results: The NRAS Q61R mutation was detected in 11 out of 60 PTC specimens (18.3%), with no statistically significant difference between patients with and without the mutation (P-value = 0.073). However, the presence of the NRAS mutation was significantly associated with encapsulated tumors (63.6%, P-value = 0.007). No significant associations were found between NRAS mutation status and other clinicopathological variables, including age, sex, PTC subtype, tumor size, multiplicity, extrathyroidal extension, or lymph node metastasis (P-value > 0.05). Conclusion: The NRAS Q61R mutation was detected at a low frequency in PTC and was significantly associated only with encapsulated tumors. No correlation was found with aggressive features, suggesting a limited role in tumor progression. Further studies with larger sample sizes are recommended to clarify its clinical significance.