SAT-337 Utility of BRAFV600E Immunohistochemistry in Differentiated Thyroid Carcinoma

Abstract Disclosure: M.R. Graff: None. A. Fingeret: None. O. Shats: None. C. Zheng: None. B. Swanson: None. W.S. Goldner: None. A. Kotwal: None. Background: Differentiated thyroid carcinoma (DTC), specifically papillary thyroid cancer (PTC), is the leading endocrine malignancy. BRAFV600E is the most common driver mutation in PTC and is present in approximately 60% of cases overall. Recent studies suggest using this with histologic data to predict risk of recurrence could be synergistic. The gold standard for detecting BRAFV600E in DTC has been NextGen sequencing. Efforts have been made to screen the tumors first with immunohistochemistry (IHC), which is quick, inexpensive, and easily implemented compared to its counterpart, and this method was used for data collection in this study. Methods: We obtained paraffin embedded DTC tissue, created Tissue microarrays, then performed IHC for BRAFV600E mutation. BRAFV600E expression was calculated using an H-score: the staining intensity (0-3) multiplied by the amount of tumor that stained positive. H-score >0 was considered positive for BRAFV600E. Clinicopathologic features including extrathyroidal extension, angiolymphatic invasion (ALI), lymph node (LN) ratio (number of positive LN/total LN removed), tumor size, AJCC stage, response to therapy, and structural recurrence were evaluated for association with BRAFV600E mutation. To compare the distribution of variables between positive and non-positive H score groups, Chi-square test, t-test, and log-rank test were used for categorical, continuous, and time-to-event variables, respectively. Results: We evaluated 234 DTC specimens with IHC. BRAFV600E mutation was detected in 109 (66%) of the 166 PTC, 21(41%) of 51 follicular variant PTC, 1 (100%) of 1 tall cell variant of PTC, 2 (18%) of 11 FTC, and 1 (20%) of 5 oncocytic carcinoma specimens. Factors including LN ratio [0.21 (SD=0.32) vs 0.12 (SD=0.26), p=0.002], number of LN removed [10.56 (SD=17.2) vs 5.02 (SD=9.85), p<0.001], and presence of ALI (p=0.015) were significantly associated with BRAFV600E mutation. When stratified by age, the association of BRAFV600E with LN ratio was not significant in age <55 years but remained significant in age ≥ 55 years. In the age ≥ 55 years group, BRAFV600E was significantly associated with the presence of Hashimoto’s thyroiditis (p=0.02). BRAFV600E was not significantly associated with AJCC stage, ATA risk category, response to therapy, structural recurrence, and overall survival. Conclusions: The high frequency of BRAFV600E mutation detected in PTC and its association with LN ratio demonstrate that IHC is a reliable tool for detecting BRAFV600E in DTC. This strengthens the feasibility of using IHC for rapid results when necessary to complement or replace NextGen sequencing. In this cohort of DTC, BRAFV600E was associated with histopathological aggressiveness but did not translate to differences in response to therapy or survival, supporting the need for incorporating other clinicopathological and molecular factors. Presentation: Saturday, July 12, 2025