Aberrant expression of lymphoid enhancer–binding factor 1 in Hodgkin lymphoma

Lymphoid enhancer–binding factor 1 (LEF1) is a transcription factor involved in T-cell maturation and is usually absent in mature B cells. Previous studies have shown aberrant LEF1 expression as a sensitive and specific marker in chronic lymphocytic leukemia/small lymphocytic lymphoma. Our primary aims were i) to analyze LEF1 expression in classic Hodgkin lymphomas (CHLs), including de novo and Richter syndrome (RS), and to assess if LEF1 can be a surrogate marker to assess clonal relationship in RS and ii) to compare LEF1 expression in CHL and nodular lymphocyte–predominant Hodgkin lymphoma (NLPHL). We included 117 patients: 24 CHL-RS, 66 CHL-de novo, and 27 NLPHL. There was no significant difference in LEF1 expression between CHL-RS and CHL-de novo (79.2% vs 87.9%, P = 0.299) or in type I and type II CHL-RS (75% vs 81.3%, P = 1.000). However, CHL showed a significantly higher LEF1 expression than NLPHL (85.6% vs 44.4%, P < 0.0001). As the Wnt/β-catenin pathway directly regulates LEF1 expression in a β-catenin-dependent way, β-catenin expression was assessed in 76 cases and all were negative. Additionally, no association between Epstein-Barr virus positivity and LEF1 expression was detected. Overall, our findings show high LEF1 expression in CHL, regardless of RS or de novo, indicating LEF1 cannot be utilized as a surrogate marker to suggest clonal relationship in RS. Compared with CHL, LEF1 expression is significantly less common in NLPHL, further attesting that they are biologically distinct entities. The absent β-catenin expression suggests LEF1 expression is independent of Wnt/β-catenin signaling pathway in Hodgkin lymphomas.