TY - JOUR
T1 - Malignant B cells from patients with primary central nervous system lymphoma express stromal cell-derived factor-1
AU - Smith, Justine R.
AU - Falkenhagen, Katherine M.
AU - Coupland, Sarah E.
AU - Chipps, Timothy J.
AU - Rosenbaum, James T.
AU - Braziel, Rita M.
PY - 2007/4
Y1 - 2007/4
N2 - 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.
AB - 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.
KW - B cell
KW - CCL20
KW - CXCL12
KW - CXCR4
KW - Immunohistochemistry
KW - Primary central nervous system lymphoma
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U2 - 10.1309/NUQHJ79BHWYD9TAF
DO - 10.1309/NUQHJ79BHWYD9TAF
M3 - Article
C2 - 17369141
AN - SCOPUS:34247141490
SN - 0002-9173
VL - 127
SP - 633
EP - 641
JO - American journal of clinical pathology
JF - American journal of clinical pathology
IS - 4
ER -