PB2152: BIOLOGICAL AND CLINICAL CORRELATES OF GALECTIN-3 (GAL-3) EXPRESSION IN DIFFUSE LARGE B-CELL LYMPHOMA (DLBCL)

Abstract

Background: Gal-3 is the only known member of the group of so-called chimeric galectins. It has 3 structural domains, a NH2 terminal domain with serine phosphatase activity, a repetitive collagen-like domain and a COOH terminal carbohydrate-recognizing domain. Gal-3 is thought to be involved in crucial cellular processes, including regulation of cell proliferation, apoptosis and angiogenesis. Gal-3 promotor contains NF-κB binding sites (Kadrofske et al, 1998). Gal-3 shares the BH1 domain with BCL2 and has antiapoptotic activitiy, but seems to affect different intracellular structures than BCL2 (Akahani et al, 1997). Normal memory B-cell, but not germinal-center cells, express gal-3. More than 50% of DLBCLs express gal-3, but none of Burkitt, follicular, marginal zone and small lymphocytic lymphomas (Hoyer et al, 2004). While preliminary data suggest that gal-3 + DLBCLs have inferior prognosis, its relation to other immunohistochemical markers, cell of origin (COO) and clinical characteristics of lymphomas are unknown Aims: To compare biological and clinical characteristics of gal-3 + and gal-3 – DLBCLs and thus gain insight into its biological function and clinical importance in this tumor type. Methods: We analyzed clinical characteristics (age, sex, IPI factors, response to treatment, event-free survival (EFS) and overall survival (OS)), immunohistochemical expression of gal-3, BCL2, VEGF and NF-κB (p65), and cell of origin (COO) as determined by Hans’ algorithm, in newly diagnosed DLBCL patients treated with R-CHOP or similar regimens. All markers were evaluated using commercially available monoclonal antibodies. Results: 123 patients were included in the study with a median follow-up of survivors of 68 months. Gal-3 was positive in 69 (56.1%), negative in 51(41.4%) and undetermined in 3. Patients with higher IPI, non-GC subtype and NF-κB + expressed gal-3 more frequently (Table). In univariate analysis gal-3 expression was not a statistically significant prognostic factor for OS and EFS in the whole group of patients (p=0.16 for EFS and p=0.19 for OS). However, BCL2 + patients fared significantly worse if they coexpressed gal-3 (EFS at 2 y 44% vs 73% (p=0,002) OS at 2 y 50% vs 74% (p=0,006)). Gal-3 expression had no influence on the outcome of BCL2- patients. In multivariate analysis of influence of immunohistochemical markers on EFS and OS, BCL2 was the only significant factor, while gal-3 showed a strong trend (p=0.068 for EFS and 0.093 for OS). If IPI was introduced into the model, gal-3 expression lost its significance. Image:Summary/Conclusion: Our results are in accordance with experimental data indicating that NF-κB stimulates gal-3 expression and that gal-3 potentiates the antiapoptotic effect of BCL2. Gal-3 is more frequently expressed in advanced-stage DLBCLs and those of non-GC subtype, consistent with its putative proliferative/antiapoptotic effect and its expression in memory B- but not germinal-center cells.