Pilot Study on the BRAF (V600E) and RAS Gene Mutations in Thyroid Tumors

Abstract Background: Thyroid cancer accounts for over 92% of endocrine malignancies, and its incidence has been steadily rising in recent years. This increase has led to significant research focused on understanding the molecular mechanisms involved in thyroid tumor development. Among the key genetic alterations associated with thyroid cancers are mutations in the BRAF gene, particularly the BRAFV600E mutation, as well as mutations in the RAS gene family (including HRAS, KRAS, and NRAS). These mutations are known to play distinct roles in the development and progression of various thyroid cancer subtypes. Objective: The study aimed to analyze the frequency of BRAF V600E and RAS mutations in thyroid tumors using real-time polymerase chain reaction (PCR). It also sought to evaluate the sensitivity and specificity of immunohistochemistry (IHC) using a mutation-specific anti-BRAFV600E monoclonal antibody (VE1) as a diagnostic tool. Materials and Methods: A total of 50 thyroid tumor cases were included in the study. All samples underwent molecular screening by real-time PCR to detect the presence of BRAF and RAS mutations. Additionally, IHC staining was performed using the anti-BRAFV600E monoclonal antibody (VE1) to detect the presence of the BRAF V600E mutation in tissue sections. Results: The study found that BRAF V600E mutations were present in 56% of papillary thyroid carcinoma cases, showing a strong association with this subtype. In contrast, RAS mutations were detected in 16.7% of cases, specifically in follicular adenomas and follicular carcinomas. A significant correlation was established between BRAF V600E mutations and papillary carcinoma diagnosis, while RAS mutations were associated with follicular-patterned tumors. The IHC method demonstrated 90% sensitivity and 100% specificity in detecting BRAF V600E mutations. No significant correlations were found between BRAF V600E mutation status and various clinicopathological parameters. Conclusion: The BRAF V600E mutation-specific monoclonal antibody (VE1) exhibited high sensitivity and specificity, indicating that immunohistochemistry is a cost-effective and reliable screening method for detecting BRAF V600E mutations in thyroid tumors. This approach may be especially useful in routine diagnostic practice to guide targeted therapy and improve patient management.