CXCR4 expression in neuroblastoma primary tumors is associated with clinical presentation of bone and bone marrow metastases.

The chemokine receptor, CXCR4, has been implicated in the mechanism of tumor cell metastasis to bone and bone marrow. Neuroblastoma, a cancer of children, is well known for its potential to metastasize to these sites. The goal of this study was to investigate whether the degree of expression of CXCR4 on cells from neuroblastoma primary tumors was related to the pattern of metastatic involvement. Archived neuroblastoma primary tumor samples and clinical data were collected from 26 patients with newly diagnosed neuroblastoma. Expression of CXCR4 (12g5 antibody) was evaluated on formalin-fixed paraffin-embedded tumor tissues using standard immunohistochemical techniques. Each tumor was graded (grade 1 through 4) based on the proportion of cells that were positive for the 12g5 antibody. Tumor grades for CXCR4 expression were compared with clinical data from each patient. Higher grades of expression (grade 3 and 4) were found in tumors from patients with high-stage disease (P < .01) and in patients with bone and bone marrow metastases (P < or = .01). Clinical outcome in patients with tumors highly expressing CXCR4 was significantly worse (P < .01) than in those patients with low-grade CXCR4. CXCR4 expression in neuroblastoma primary tumors is significantly correlated with the pattern of metastatic spread.