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

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 y 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 = .008 HR = 23.4]) and PFS (P = .005 HR = 34.0]). Risk was divided by B symptoms (P = .001 OS]; P = .034 PFS]) in low IPI subset (n = 36), and by A20 deletion (P = .029 PFS]) in high IPI subset (n = 13). These results suggest a clinicopathologic implication of A20 in progression of NKTL.