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

Justine R. Smith, Katherine M. Falkenhagen, Sarah E. Coupland, Timothy J. Chipps, James T. Rosenbaum, Rita M. Braziel

Research output: Contribution to journalArticle

40 Scopus citations

Abstract

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-3α (MIP-3α, 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 of MIP-3α 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.

Original languageEnglish (US)
Pages (from-to)633-641
Number of pages9
JournalAmerican journal of clinical pathology
Volume127
Issue number4
DOIs
StatePublished - Apr 1 2007

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Keywords

  • B cell
  • CCL20
  • CXCL12
  • CXCR4
  • Immunohistochemistry
  • Primary central nervous system lymphoma

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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