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K.M. Falkenhagen, R.M. Braziel, S.E. Coupland, J.T. Rosenbaum, J.R. Smith; Expression of Stromal Cell–Derived Factor–1 in Primary Central Nervous System Lymphoma . Invest. Ophthalmol. Vis. Sci. 2005;46(13):1002.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose:Although the pathogenesis of primary central nervous system lymphoma (PCNSL) remains unclear, it is hypothesized that specific chemokine–chemokine receptor interactions may contribute to localization of malignant B lymphocytes to the eye and brain. One candidate mediator is the lymphoid chemokine, stromal cell–derived factor–1 (SDF–1; CXCL12). Although initial work focused on its critical role in hematopoiesis, more recently the participation of SDF–1 in neural development has been recognized; SDF–1 is constitutively expressed by brain neurons and endothelium, neuroglia and meningeal cells. Consequently, we studied the expression of this chemokine in PCNSL. Methods: Formalin–fixed, paraffin–embedded brain biopsy specimens from 5 patients with PCNSL were cut 3 microns in thickness and stained by standard indirect immunohistochemical methods, using a goat polyclonal anti–human SDF–1 antibody (Santa Cruz Biotechnology) at a concentration of 10 µg/mL. Following deparaffinization of the tissue, antigen retrieval was performed by boiling the sections for 10 minutes in 10 mM citrate buffer at pH 6.0. Normal tonsil, and astrocytoma and meningioma biopsies were also immunostained. Negative controls were prepared by substituting goat IgG (Sigma) for the specific antibody. Results: Positive staining for SDF–1 was identified in all 5 of the PCNSL biopsy specimens. Within the lymphoma, SDF expression was localized to neurons, endothelial cells and meningeal cells. Weaker staining was also observed in lymphoma cells that were either diffusely distributed through the brain tissue or present as perivascular infiltrates. Neuronal and meningeal expression of SDF–1 was noted in the astrocytoma and meningioma biopsies; tonsil stained positively for SDF–1 in the crypt and outer epithelium, and within the tonsil proper. Negative controls showed no positive staining. Interestingly, a mouse monoclonal anti–human SDF–1 antibody (R&D Systems) that recognized SDF–1 in tonsil showed no reactivity in either normal brain or PCNSL biopsy specimens. Conclusions: Expression of SDF–1 occurs within PCNSL lesions in the brain, as well as normal brain tissue. Studies examining the functional relevance of this expression are indicated to assess possible involvement of SDF–1 in the pathogenesis of PCNSL.
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