BRAF V600E Mutation in Chinese Patients with Langerhans Cell Histiocytosis and Its Clinical Significance

Abstract

To investigate the BRAF V600E mutation in Chinese patients with langerhans cell histiocytosis (LCH) and its clinical significance. The clinical records of 50 pathology-diagnosed LCH cases were analyzed retrospectively and the Paraffin-embedded tissue blocks were retrieved to test the BRAF V600E mutation by immunohistochemical method with a specific BRAF V600E protein antibody. BRAF V600E mutation was also tested by High-resolution Melting Analysis (HRM) followed by Sanger sequence in 31 cases. BRAF V600E mutation was found in 58% (29/50) LCH cases by gene test or protein test. BRAF V600E expression was identified in 56% (28/50) LCH cases by immunohistochemical analysis alone while 54.8% (17/31) by HRM-Sanger alone. Two out of 14 cases, who were negative for BRAF V600E by HRM-Sanger analysis, were positive by immunohistochemical tests (14.3%). Otherwhile, only 1 out of 17 LCH cases with a positive BRAF V600E mutation by gene test were negative by immunohistochemical analysis. The status of BRAF V600E did not show significant relevance with age, sex, clinical stage or response. Also, BRAF V600E had no effect on the 3-year survival or event-free survival in this group. Immunohistochemical tests for BRAF V600E in Paraffin-embedded tissue is of ideal sensitivity, 58% Chinese LCH patients have BRAF V600E positive and so LCH is a clonal disease but the exact role of BRAF V600E in LCH needs further research.