Immunoexpression of Mutated BRAF V600E Protein in Papillary Thyroid Carcinoma

Abstract

Background and Objectives: In papillary thyroid cancer (PTC), BRAF V600E is the most prevalent genetic alteration, and in different populations, its frequency ranges from 29% to 83%. BRAF mutation is mostly detected by DNA-based molecular methods, which are labor-intensive and time-consuming. A method, immunohistochemistry (IHC), was recently introduced to detect BRAF-mutated proteins. This method enables a monoclonal BRAF V600E mutation-specific antibody that can distinguish BRAF V600E from wild-type protein in conventionally processed, formalin-fixed, paraffin-embedded tissue and the mutant protein that was directly visualized in tumour cells in a tissue context. This study aimed to determine the BRAF V600E-mutated protein's immunoexpression in papillary thyroid carcinoma. Methodology: The study was a laboratory-based cross-sectional descriptive study. A total of 44 histologically proven paraffin-embedded tissue blocks of PTC were collected. Anti-BRAF V600E rabbit monoclonal primary antibody was used for immunohistochemistry on tissue sections, and the staining intensity was scored from 0 to 3 (+): 0, no cytoplasmic staining in tumour cells; 1: faint cytoplasmic staining in over 10% of tumour cells; 2+, moderate cytoplasmic staining in over 10% of tumour cells; 3+, strong cytoplasmic staining in over 10% of tumour cells. Tumour cells with a score of 1+, 2+, or 3+ were considered positive for mutated BRAF V600E immunoexpression, and those with a score of 0 were considered negative. Results: Among 44 cases, 34 (77.3%) were positive, and 10 (22.7%) were negative for the mutated BRAF V600E protein by IHC staining. In terms of staining intensity, 4 (9.1%), 20 (45.5%), and 10 (22.7%) cases had IHC scores of 1+, 2+, and 3+, respectively. This study reported a high-frequency rate (77.3%) of mutated BRAF protein, similar to the frequency reported in other Asian countries. There was no association between mutated BRAF V600E protein status and either age or gender. Conclusion: The most effective PTC diagnostic marker is BRAF V600E mutation. The IHC technique using BRAF V600E mutation-specific antibodies is relatively simple and faster and is therefore proposed as the most reliable first-line method for detecting BRAF V600E-mutated proteins.