Immunoexpression of Mutated BRAF V600E Protein in Papillary Thyroid Carcinoma
Ohnmar Than *
Department of Medical Laboratory Technology, University of Medical Technology, Yangon, Myanmar.
Mie Mie Than
Department of Medical Laboratory Technology, University of Medical Technology, Yangon, Myanmar.
Le՝Shwe Zin
Department of Pathology, University of Medicine (2), Yangon, Myanmar.
Nyo Me May Thyn
Department of Pathology, University of Medicine (2), Yangon, Myanmar.
*Author to whom correspondence should be addressed.
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.
Keywords: Myanmar, immunohistochemistry (IHC), BRAF V600E, papillary thyroid carcinoma, formalin-fixed paraffin-embedded tissue, monoclonal antibody, cytoplasmic staining
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