Comparison of the expression and prognostic significance of differentiation markers between diffuse large B-cell lymphoma of central nervous system origin and peripheral nodal origin.

Abstract

Purpose: Whether diffuse large B-cell lymphoma (DLBCL) of primary central nervous system origin (PCNSL) is biologically different from DLBCL of peripheral nodal origin (NL) remains unclear. The purpose of this study was to compare the expression frequencies and prognostic significance of a panel of cell differentiation markers between these two disease entities. Experimental Design:This study included HIV-unrelated patients with PCNSL (n = 51) and NL (n = 72) treated at four hospitals inTaiwan for whom archival tumor tissue was available. Immunohistochemistry for CD10, BCL-6, MUM-1, vs38c, CD138, and BCL-2 was done. CD10, BCL-6, and MUM-1expression results were used to classify all cases into the germinal center B-cell (GCB) or the non-GCB subgroup. The prognostic significances of clinical and immunophenotypic markers were evaluated.Results: Nuclear MUM-1expression was significantly higher in PCNSL than in NL (P < 0.001; 84% versus 53%). PCNSL tumors were more frequently classified into the non-GCB subgroup than NL tumors (P = 0.020; 78% versus 62%). For patients with PCNSL, univariate analysis showed that patients with BCL-6 expression had a trend towards longer survival (P = 0.073; median survival, 25.3 versus 7.3 months), and multivariate analysis showed BCL-6 was an independent prognostic factor (P = 0.026). For patients with NL, both of univariate (P = 0.003) and multivariate analyses (P = 0.002) showed that GCB was significantly associated with favorable survival. Conclusion: The higher frequency of non-GCB subclassification, which was mainly contributed by nuclear MUM-1expression in PCNSL implies that it has a more differentiated cellular origin than NL. BCL-6 expression in patients with PCNSL and GCB subgroup in patients with NL were favorable prognostic factors.

Evaluation of BCL-6, CD10, CD138 and MUM-1 Expression in Diffuse Large B-Cell Lymphoma patients: CD138 is a Marker of Poor Prognosis

“…Harada et al, 1999;Braaten et al, 2003;Berglund et al, 2005;Sjo et al, 2007), whereas nine studies did not report any significant difference in OS between positive and negative BCL-6 expression in DLBCL patients (e.g. Colomo et al, 2003;Kojima et al, 2006;Lin et al, 2006;Muris et al, 2006). A study by Winter et al (2006), reported a significantly increased OS in DLBCL patients with positive BCL-6 expression that were treated with the CHOP regimen, but no difference in OS related to BCL-6 expression in patients treated with R-CHOP.…”

“…Of these studies, six reported significant association between positive MUM-1 expression and decreased OS (Chang et al, 2004;Hans et al, 2004;Lin et al, 2006;Muris et al, 2006;Hallermann et al, 2007;Liu et al, 2008), while ten failed to find a significant difference in OS between patients with positive and negative MUM-1 expression (e.g. Berglund et al, 2005;Kojima et al, 2006;Oh and Park, 2006;Sjo et al, 2007).…”

“…Berglund et al, 2005;Kojima et al, 2006;Oh and Park, 2006;Sjo et al, 2007). Three out of these ten studies (Braaten et al, 2003;Camilleri-Broet et al, 2006;Lin et al, 2006) scored seven or fewer negative samples for MUM-1 expression, severely reducing the statistical power of testing in these studies. Other studies, however, had considerable sample sizes of both MUM-1 positive and MUM-1 negative DLBCL patients and still failed to detect a significant difference in the survival of the two groups (Colomo et al, 2003;Saez et al, 2004;Berglund et al, 2005;Hoffmann et al, 2005;Sjo et al, 2007).…”

Diffuse large B-cell lymphoma: a heterogeneous group of non-Hodgkin lymphomas comprising several distinct clinicopathological entities

“…66 The clinical behavior and prognosis of these lymphomas is not only influenced by the anatomic location but apparently also by biological factors (ABC-like versus GCB-like tumors with different underlying oncogenic mechanisms). Immunohistochemical expression of bcl-6 in PCNSL is found to be associated with a longer OS.…”

Pathology of primary central nervous system lymphoma

“…6,13 A number of studies have shown expression of Bcl-6 protein in most diffuse large B-cell PCNSLs. 6,26,27 A majority (85%) also are positive for an activation marker of late germinal center/early postgerminal center B cells (MUM-1). 6,27 A few expressed vs38c, a marker for plasma cells, but all were negative for CD138, another marker of plasmacytic differentiation.…”