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Prepublished online as a Blood First Edition Paper on October 3, 2002; DOI 10.1182/blood-2002-05-1576.

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Blood, 1 February 2003, Vol. 101, No. 3, pp. 815-821

CHEMOKINES

Expression of B-cell-attracting chemokine 1 (CXCL13) by malignant lymphocytes and vascular endothelium in primary central nervous system lymphoma

Justine R. Smith, Rita M. Braziel, Samantha Paoletti, Martin Lipp, Mariagrazia Uguccioni, and James T. Rosenbaum

From the Casey Eye Institute and Department of Pathology, Oregon Health and Science University, Portland, OR; Institute for Research in Biomedicine, Bellinzona, Switzerland; and Max-Delbrueck-Center for Molecular Medicine, Berlin-Buch, Germany.

Primary central nervous system lymphoma (PCNSL) is a rare but often rapidly fatal form of non-Hodgkin B-cell lymphoma that arises within the central nervous system (CNS) and has a low propensity to metastasize. We performed immunohistochemistry on formalin-fixed, paraffin-embedded brain biopsy specimens from 24 patients with PCNSL to investigate the expression of B cell-attracting chemokine 1 (BCA-1, CXCL13), a lymphoid chemokine involved in B-cell compartmental homing within secondary lymphoid organs and recently implicated in the pathogenesis of inflammatory and malignant lymphocyte-mediated diseases. Whereas BCA-1 was not detected in normal human brain, all 24 brain biopsy specimens containing PCNSL were positive for BCA-1. Double immunostaining on selected specimens localized BCA-1 to malignant B lymphocytes and vascular endothelium. In contrast, 2 chemokines implicated particularly in T-cell movement, secondary lymphoid tissue chemokine (SLC, CCL21) and Epstein-Barr virus-induced molecule 1 ligand chemokine (ELC, CCL19), were expressed only by occasional stromal cells in 2 and 4 of the 24 specimens, respectively. Tumor cells stained positively for CXCR5, the primary receptor for BCA-1. In situ hybridization verified the expression of BCA-1 mRNA by malignant B cells, but not vascular endothelium, within the tumor mass, suggesting that vascular endothelial BCA-1 expression may be consequent to transcytosis. In PCNSL, expression of BCA-1 by malignant lymphocytes and vascular endothelium may influence tumor development and localization to CNS.

© 2003 by The American Society of Hematology.
 

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