BMI‐1 protein expression as a negative independent prognostic factor in DLBCL

Abstract

Introduction: The BMI-1 gene belongs to the polycomp group family and was originally identified as a proto-oncogene during lymphoma development. In diffuse large B-cell lymphoma (DLBCL), high BMI-1 gene expression can be used in distinguishing cell of origin (COO). Expression of BMI-1 protein in DLBCL is however poorly investigated. We aimed to investigate if BMI-1 protein expression was a prognostic factor in a consecutive cohort of patients with DLBCL. Methods: All patients with DLBCL diagnosed and treated 2009-2011 at Copenhagen University Hospital Herlev were collected consecutively and classified according to morphology and COO by immunohistochemistry (IHC, Hans algorithm). BMI-1 protein expression was investigated retrospectively by IHC. A total of 212 patients (163 primary + 49 transformed DLBCL) were included—176 of the patients had received intensive chemotherapy (R-CHOP/R-CHOEP in 174 patients). Results: Tissue was available for BMI-1 analysis in 162 patients. Median BMI-1 expression was 40% with IQR 10-80%. High BMI-1 expression ≥80% was seen in 32% (52/162) of patients and in 30% (42/139) of the patients whom had been intensively treated. Treatment regimens were comparable between patients with high and low BMI-1 expression. A tendency towards an associations between high BMI-1 expression and nonGCB profile (P = .07) and transformed lymphoma (P = .07) was observed (chi-square). High BMI-1 expression was not associated with bone marrow involvement (P = .5), extra nodal involvement (P = .2), performance status (P = .3), IPI score (P = .9), Ann Arbor stage (P = .14), or proliferation rate (P = .7) (chi-square). High BMI-1 expression had negative prognostic impact on both PFS and OS in univariate survival analysis (log rank); PFS (HR 1.9, P = .003), OS (HR 1.6, P = .04) (figure). In multivariable analysis (Cox proportional hazards models) including IPI, COO, and BMI-1 ≥80, both high BMI expression (PFS [HR 2.3, P = .001] and OS [HR 1.9, P = .009]) and IPI (PFS [HR 1.7, P = .001] and OS [HR 1.8, P = .001]) were independent prognostic factors. This was also seen in the subgroup of intensively treated patients. In univariate analysis, similar trends were seen when only patients with primary DLBCL were included. Keywords: diffuse large B-cell lymphoma (DLBCL); prognostic indices