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

Am J Clin Pathol. 2019 Jul 5;152(2):243-252. doi: 10.1093/ajcp/aqz041.

Abstract

Objectives: To investigate the role of TNFAIP3 deletions and NF-κB activation in extranodal natural killer/T-cell lymphoma (ENKTCL), nasal type.

Methods: In total, 138 patients with ENKTCL were included. Activation of NF-κB 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-κB 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-κB pathway activation or TNFAIP3 heterozygous deletion to have a longer overall survival.

Conclusions: Our study demonstrated that NF-κB activation and TNFAIP3 heterozygous deletion confer superior survival in patients with ENKTCL.

Keywords: Extranodal NK T cell; Lymphoma; NF-κB; Prognosis; Tumor necrosis factor alpha-induced protein 3.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Child
  • Female
  • Gene Deletion
  • Humans
  • Lymphoma, Extranodal NK-T-Cell / genetics*
  • Lymphoma, Extranodal NK-T-Cell / metabolism
  • Lymphoma, Extranodal NK-T-Cell / mortality
  • Lymphoma, Extranodal NK-T-Cell / pathology
  • Male
  • Middle Aged
  • NF-kappa B / metabolism*
  • Prognosis
  • Signal Transduction / physiology*
  • Survival Rate
  • Tumor Necrosis Factor alpha-Induced Protein 3 / genetics*
  • Tumor Necrosis Factor alpha-Induced Protein 3 / metabolism
  • Young Adult

Substances

  • NF-kappa B
  • TNFAIP3 protein, human
  • Tumor Necrosis Factor alpha-Induced Protein 3