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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.

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