Clinicopathologic implications of TNFAIP3/A20 deletions in extranodal NK/T-cell lymphoma

Abstract

The A20/Tumor necrosis factor-alpha-induced protein 3 (A20/TNFAIP3) is a negative regulator of NF-κB signaling. We analyzed the clinicopathologic implications of A20 deletions in extranodal NK/T-cell lymphoma (NKTL). Fluorescence in situ hybridization analysis of the A20 gene was performed using archived formalin-fixed tissues in 49 cases of NKTL. Among the 49 NKTL patients (median age, 48 years [10-79]), stage I-II (75% [36/48]) and upper aerodigestive tract (UAT)-origin (84% [41/49]) were predominant. All A20 deletions were monoallelic and found in cases with UAT-origin, accounting for 18% (9/49) of all NKTLs and 22% (9/41) of UAT-origin. In univariate analysis, overall survival (OS) and progression-free survival (PFS) were associated with stage, international prognostic index (IPI), B symptoms and number of extranodal sites, and OS with performance status and non-UAT-origin, but none with A20 deletion. In multivariate analysis, IPI predicted OS (P=0.008 [HR=23.4]) and PFS (P=0.005 [HR=34.0]). Risk was divided by B symptoms (P=0.001 [OS]; P=0.034 [PFS]) in low IPI subset (n=36), and by A20 deletion (P=0.029 [PFS]) in high IPI subset (n=13). These results suggest a clinicopathologic implication of A20 in progression of NKTL. This article is protected by copyright. All rights reserved.

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