Expression of B-cell-attracting chemokine 1 (CXCL13) by malignant lymphocytes and vascular endothelium in primary central nervous system lymphoma.
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.
Smith
Justine R
JR
Casey Eye Institute and Department of Pathology, Oregon Health and Science University, Portland, OR 97201, USA. smithjus@ohsu.edu
Braziel
Rita M
RM
Paoletti
Samantha
S
Lipp
Martin
M
Uguccioni
Mariagrazia
M
Rosenbaum
James T
JT
D000328:Adult; D000368:Aged; D001921:Brain / Q000473:pathology; D016022:Case-Control Studies; D016543:Central Nervous System Neoplasms / Q000378:metabolism* / Q000473:pathology; D054415:Chemokine CCL19; D054421:Chemokine CCL21; D054382:Chemokine CXCL13; D019742:Chemokines, CC / Q000032:analysis; D019743:Chemokines, CXC / Q000096:biosynthesis* / Q000235:genetics; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008214:Lymphocytes / Q000378:metabolism* / Q000473:pathology; D008223:Lymphoma / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis; D054380:Receptors, CXCR5; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine / Q000032:analysis
C515460:CCL19 protein, human; C515478:CCL21 protein, human; C110663:CXCL13 protein, human; C095085:CXCR5 protein, human; D054415:Chemokine CCL19; D054421:Chemokine CCL21; D054382:Chemokine CXCL13; D019742:Chemokines, CC; D019743:Chemokines, CXC; D012333:RNA, Messenger; D054380:Receptors, CXCR5; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine