Tumor angiogenesis correlates with metastatic disease, N-myc amplification, and poor outcome in human neuroblastoma

Abstract

Purpose: To determine if the clinical outcome of children with neuroblastoma (NB) is correlated with the degree of tumor neovascularization and to assess the relationship of stage, N-myc copy number, and histology to angiogenesis.

Materials and methods: The vascularity of primary untreated NB from 50 patients diagnosed at a single institution between 1984 and 1994 was evaluated. An image processor was used to analyze the tumor tissue area for each histologic slide of tumor, and a vascular index (VI) was calculated, where VI = total number of vessels/mm2 of tissue area. Tumors were classified histologically according to the criteria of Shimada et al (J Natl Cancer Inst 73:405-416, 1984), and N-myc copy number was determined by Southern blot analysis.

Results: We found that higher VI (> 4.0) in NB strongly correlated with widely disseminated disease (P = .006) and poor survival (P < .0001). VI more than 4.0 was also statistically associated with N-myc amplification (P = .02) and unfavorable histology (P = .02). Univariate analysis demonstrated that disease stage, tumor histology, and N-myc copy number were also predictive of outcome. Cox regression analysis showed that VI provided independent prognostic information.

Conclusion: Our studies indicate that angiogenesis may play an important role in determining the biologic behavior of NB. Antiangiogenic therapy may prove to be effective in the treatment of children with highly vascular, widely disseminated NB.