Malignant B cells from patients with primary central nervous system lymphoma express stromal cell-derived factor-1.

Although the pathogenesis of primary central nervous system lymphoma (PCNSL) remains unclear, it is hypothesized that specific chemokine-chemokine receptor interactions may attract malignant B lymphocytes into the CNS. Formalin-fixed, paraffin-embedded brain biopsy specimens from 40 patients with PCNSL were immunostained by an indirect immunohistochemical method incorporating antigen retrieval to detect the presence of B-cell chemokines, stromal cell-derived factor-1 (SDF-1; CXCL12) and macrophage inflammatory protein-3alpha (MIP-3alpha, CCL20), and the SDF-1 receptor, CXCR4. To assist in phenotyping of SDF-1 + cells, specimens were also stained for CD20 (B cells). Positive staining for SDF-1 was identified in all PCNSL cases and in tonsil. In biopsy specimens, SDF-1 expression was localized to resident brain cells and, in 80% of specimens, CD20+ malignant lymphocytes. Tumor cells also stained positively for CXCR4. In contrast, although expression ofMIP-3alpha was detected in tonsil, no expression of this chemokine could be demonstrated in PCNSL biopsy specimens. Our observations raise the possibility of targeting the SDF-1-CXCR4 signaling pathway as a potential treatment for PCNSL.

Expression of vascular endothelial growth factor and its receptors in rosacea.

BACKGROUND: Rosacea is a common chronic disease of unclear pathogenesis, characterised by inflammation and vascular abnormalities of the facial skin and ocular surface. Recognising that vascular endothelial growth factor (VEGF) is vasoactive and has inflammatory activities, the expression of this molecule and its receptors, VEGF-R1 and VEGF-R2, in rosacea was investigated. METHODS: Formalin-fixed, paraffin wax-embedded sections of skin obtained from 20 patients with rosacea were immunostained to detect expression of VEGF, VEGF-R1 and VEGF-R2, using an indirect methodology incorporating antigen retrieval. Adjacent sections were stained with haematoxylin and eosin. RESULTS: Biopsy specimens were characterised by perivascular and perifollicular lymphohistiocytic infiltration and dilated vascular channels. In addition to keratinocyte and epithelial staining, which was also noted in normal skin, vascular endothelium frequently stained positive for VEGF-R1 (14/20, 70%) and VEGF-R2 (20/20, 100%), but infrequently for VEGF (2/20, 10%). In most specimens, infiltrating leucocytes, including lymphocytes, macrophages and plasma cells, expressed VEGF (17/20, 85%), VEGF-R1 (20/20, 100%) and VEGF-R2 (20/20, 100%). CONCLUSION: Expression of VEGF receptors, both by vascular endothelium and infiltrating mononuclear cells, is observed in rosacea. Although not expressed by endothelium, VEGF is present in epidermis and epithelium, and is expressed by infiltrating cells. VEGF receptor-ligand binding may contribute to the vascular changes and cellular infiltration that occurs in rosacea.

B-Cells in ocular adnexal lymphoproliferative lesions express B-cell attracting chemokine 1 (CXCL13).

PURPOSE: The homeostatic chemokine, B cell attracting chemokine 1 (CXCL13), has been implicated in the pathogenesis of lymphocyte-mediated diseases. We investigated the cellular expression of this chemokine in the spectrum of ocular adnexal lymphoproliferative lesions. DESIGN: Laboratory investigation. METHODS: CXCL13 expression in paraffin-embedded adnexal biopsy specimens was determined by indirect immunohistochemistry with antigen retrieval. RESULTS: In 15 of 16 biopsy specimens, including reactive lymphoid hyperplasia (n = 7), atypical lymphoid hyperplasia (n = 3), and B cell lymphoma (n = 6), CXCL13 was detected. CD20-positive B-cells, as well as dendritic cells and endothelial cells, expressed the chemokine. CONCLUSIONS: B-cells in ocular adnexal lymphoproliferative lesions demonstrate expression of CXCL13, a chemokine that may participate in tumor pathogenesis and is a potential target for novel therapies.