Sarcoidosis is not associated with BRAFV600E mutation

Purpose/Aim of the study: BRAFV600E is an oncogenic point mutation in the MAPK/ERK signaling pathway, which is important for cell proliferation and migration. It has been found to be associated with several malignancies and has also been found in significant proportions of patients with Langerhans cell histiocytosis. A recent mouse model which introduces the BRAFV600E mutations only into dendritic cell precursors results in a clinical picture very similar to human sarcoidosis. We therefore hypothesized that somatic BRAFV600E mutations may play a role in granuloma formation and/or maintenance in all or a subset of patients with sarcoidosis. Materials and methods: 28 diagnostic lymph node samples and 1 diagnostic lung parenchyma sample of patients with confirmed sarcoidosis were identified. Paraffin sections including positive and negative controls were stained using pre-diluted Ventana Medical Systems anti-BRAF V600E (VE1) mouse monoclonal antibody and processed on an automated Ventana Benchmark Ultra immunostainer. Slides were analyzed by two independent experts. Results: BRAFV600E immunostaining was negative in all 29 cases. Conclusions: Sarcoidosis is not associated with the BRAFV600E mutation and is very unlikely to be associated with other less common BRAF mutations not tested for in this study. Future studies addressing a potential role of other somatic mutations in cell proliferation and migration pathways are warranted. Subjects: Immunology; Medical Genetics; Pulmonary Medicine