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JR Smith, RM Braziel, M Uguccioni, S Paoletti, EA Neuwelt, JT Rosenbaum; BCA-1 And Its Receptor, CXCR5, Are Expressed In Primary Central Nervous System Lymphoma (PCNSL): In Situ Hybridization And Immunohistochemical Observations . Invest. Ophthalmol. Vis. Sci. 2002;43(13):1859.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Intraocular B cell lymphoma is frequently associated with CNS involvement, in which case the tumor is termed PCNSL. In secondary lymphoid tissues the lymphoid chemokine, BCA-1, which is expressed by follicular dendritic cells, directs the movement of B lymphocytes expressing the receptor, CXCR5. Previous immunostaining studies from our group have indicated that BCA-1 might be expressed in PCNSL, suggesting a role for this chemokine in the pathogenesis of intraocular and CNS lymphoma. We used in situ hybridization to confirm our initial observation, as well as immunostaining to identify which cells expressed BCA-1 and to demonstrate CXCR5 expression by malignant cells. Methods: We examined formalin-fixed, paraffin-embedded brain biopsy specimens from HIV-negative patients with PCNSL. In situ hybridization was performed on tissue sections (n=8 specimens), using sense and antisense probes appropriate for detection of mRNA encoding BCA-1. Additional sections (n=5 specimens) were indirectly double-immunostained, using one antibody directed against human BCA-1 and a second antibody recognizing human CD20 (B cell), CD21 (follicular dendritic cell), or CD31 (vascular endothelium). Other sections (n=6 specimens) were immunostained with anti-CXCR5 antibody. For immunohistochemistry, antigen retrieval was achieved by boiling sections in citrate buffer (BCA-1, CD20, CD31) or commercially available (DAKO) antigen retrieval solution (CXCR5), or by trypsin digestion (CD21). Results: In situ hybridization demonstrated the presence of mRNA encoding BCA-1 within the tumor mass of the biopsy specimens. The pattern of BCA-1 mRNA expression was remarkably non-uniform. Double-immunostaining localized BCA-1 to B lymphocytes and also to the vascular endothelium. Interestingly, no follicular dendritic cells were detected in the biopsies. B lymphocytes stained positively for CXCR5. Conclusion: There is ectopic expression of the B cell chemokine, BCA-1, by lymphocytes and vascular endothelium (but not follicular dendritic cells) in brain specimens from patients with PCNSL. Malignant cells within the tumor express CXCR5, supporting the hypothesis that BCA-1 may participate in tumor pathogenesis. Therapies targeting BCA-1 or its receptor may be useful in treatment of intraocular or CNS lymphoma.
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