Activation of the NF-κB Pathway and Heterozygous Deletion of TNFAIP3 (A20) Confer Superior Survival in Extranodal Natural Killer/T-Cell Lymphoma, Nasal Type.

Objectives: To investigate the role of TNFAIP3 deletions and NF-kappa B activation in extranodal natural killer/T-cell lymphoma (ENKTCL), nasal type. Methods: In total, 138 patients with ENKTCL were included. Activation of NF-kappa B pathway and expression of TNFAIP3 (A20) were examined by immunohistochemistry. TNFAIP3 was analyzed for deletions using FICTION (fluorescence immunophenotyping and interphase cytogenetics as a tool for investigating neoplasms), for mutations using Sanger sequencing, and for promoter methylation using methylation-specific sequencing. Results: NF-kappa B pathway activation was observed in 31.2% of cases (43/138), TNFAIP3 expression was negative in 15.2% of cases (21/138), and heterozygous TNFAIP3 deletion was observed in 35% of cases (35/100). TNFAIP3 exons 2 to 9 mutations and promoter methylation were not observed. Kaplan-Meier analysis showed patients with NF-kappa B pathway activation or TNFAIP3 heterozygous deletion to have a longer overall survival. Conclusions: Our study demonstrated that NF-kappa B activation and TNFAIP3 heterozygous deletion confer superior survival in patients with ENKTCL.