Abstract
Survivin is one of the inhibitors of apoptosis proteins (IAP) that might play an important role in the pathogenesis of diffuse large B cell lymphoma (DLBCL). The present study was designed to investigate the clinical and prognostic significance of survivin expression in nodal DLBCL. We analyzed lymph node biopsy specimens obtained from 56 patients with newly diagnosed nodal DLBCL, treated with immunochemotherapy (R-CHOP). The expression of survivin was analyzed using the standard immunohistochemical method on formalin-fixed and routinely processed paraffin-embedded lymph node specimens and evaluated semiquantitatively as a percentage of tumor cells. Survivin immunoexpression (>45 % positive tumor cells) was found in 22 (39.28 %) and observed as cytoplasmic staining in 15 patients, or mixed (cytoplasmic and nuclear) staining in 7 patients. A significant difference in survivin immunoexpression was noticed between the GCB and the non-GCB subtypes of DLBCL (p = 0.031). However, survivin immunoexpression had no significant association with IPI, “bulky” disease, extranodal localization, hemoglobin, Ki-67 immunoexpression or other clinicopathological parameters. A univariate analysis showed that survivin positivity was an unfavorable factor for therapy response and a predictor of shorter survival in patients with DLBCL (p = 0.048 and p = 0.034, respectively). Patients with survivin overexpression experienced a relapse more often than patients without expression of this apoptotic protein (27.3 vs. 11.8 %), but this difference did not reach statistical significance (p = 0.131). The results of this study showed that disregulation of survivin expression had an important role in the determination of the course of the disease in patients with nodal DLBCL treated with R-CHOP. Therefore, survivin represents a potential target for therapeutic intervention in DLBCL.
Highlights
Diagnosed nodal diffuse large B cell lymphoma (DLBCL) is an aggressive disease with variable clinical, histological, immunophenotypic and cytogenetic features [1]
Previous studies have shown that deregulation of apoptosis signaling cascade is an important factor in the pathogenesis of lymphoma and that such deregulation may be an important cause for chemotherapy resistance and a poor prognosis in DLBCL [7,8,9,10,11,12,13]
Previous studies have shown that deregulation of inhibitory apoptotic proteins is an important factor in the pathogenesis of lymphoma and that such deregulation may be an important cause for chemotherapy resistance and poor prognosis in DLBCL [7,8,9,10,11,12]
Summary
Diagnosed nodal diffuse large B cell lymphoma (DLBCL) is an aggressive disease with variable clinical, histological, immunophenotypic and cytogenetic features [1]. Med Oncol (2012) 29:3515–3521 survival of patients with DLBCL, some patients do not achieve a favorable therapeutic response or relapse after successful treatment [2]. Apoptosis is a genetically regulated cell death mechanism essential for the development and homeostasis of multicellular organisms. It is regulated by two families of proteins: the BCL2 family, comprising both pro- and antiapoptotic members [3], and the inhibitor of apoptosis protein (IAP) family, consisting only of anti-apoptotic molecules [4]. Inactivation of survivin expression can restore TRAIL sensitivity in resistant non-Hodgkin lymphoma B cells [6]
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