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.
OBJECTIVE
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.


METHODS
This study included HIV-unrelated patients with PCNSL (n = 51) and NL (n = 72) treated at four hospitals in Taiwan 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-1 expression 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-1 expression 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.


CONCLUSIONS
The higher frequency of non-GCB subclassification, which was mainly contributed by nuclear MUM-1 expression 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.
Lin
Ching-Hung
CH
Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan.
Kuo
Kuan-Ting
KT
Chuang
Shih-Sung
SS
Kuo
Sung-Hsin
SH
Chang
Julia Hueimei
JH
Chang
Kung-Chao
KC
Hsu
Hui-Chen
HC
Tien
Hwei-Fang
HF
Cheng
Ann-Lii
AL
D000911:Antibodies, Monoclonal / Q000032:analysis; D000943:Antigens, Differentiation / Q000032:analysis*; D001402:B-Lymphocytes / Q000737:chemistry / Q000473:pathology; D015415:Biomarkers / Q000032:analysis; D002490:Central Nervous System / Q000737:chemistry / Q000473:pathology*; D004268:DNA-Binding Proteins / Q000032:analysis; D005260:Female; D018858:Germinal Center / Q000737:chemistry / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D050835:Interferon Regulatory Factors / Q000032:analysis; D008198:Lymph Nodes / Q000737:chemistry / Q000473:pathology*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis; D008875:Middle Aged; D015260:Neprilysin / Q000032:analysis; D011379:Prognosis; D011509:Proteoglycans / Q000032:analysis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D051560:Proto-Oncogene Proteins c-bcl-6; D016019:Survival Analysis; D053668:Syndecan-1; D053667:Syndecans; D000099218:Interferon Regulatory Factor-4
D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation; D015415:Biomarkers; D004268:DNA-Binding Proteins; D050835:Interferon Regulatory Factors; D008562:Membrane Glycoproteins; D015260:Neprilysin; D011509:Proteoglycans; D019253:Proto-Oncogene Proteins c-bcl-2; D051560:Proto-Oncogene Proteins c-bcl-6; D053668:Syndecan-1; D053667:Syndecans; D000099218:Interferon Regulatory Factor-4; C084103:BCL6 protein, human; C508241:SDC1 protein, human; C100347:VS38 monoclonal antibody