TUMOR ANGIOGENESIS CORRELATES WITH METASTATIC DISEASE, N-MYC AMPLIFICATION, AND POOR OUTCOME IN HUMAN NEUROBLASTOMA

Purpose: To determine if the clinical outcome of children with neurobl astoma (NB) is correlated with the degree of tumor neovascularization and to assess the relationship of stage, N-myc copy number, and histol ogy to angiogenesis. Materials and Methods: The vascularity of primary untreated NB from 50 patients diagnosed at a single institution betwe en 1984 and 1994 wets evaluated, An image processor was used to analyz e the tumor tissue area for each histologic slide of tumor, and a vasc ular index (VI) was calculated, where VI = total number of vessels/mm( 2) of tissue area, Tumors were classified histologically according to the criteria of Shimada et al (J Natl Cancer Inst 73:405-416, 1984), a nd N-myc copy number was determined by Southern blot analysis. Results : We found that higher VI (> 4.0) in NE strongly correlated with widel y disseminated disease (P = .006) and poor survival (P < .0001). VI mo re than 4.0 was also statistically associated with N-myc amplification (P = .02) and unfavorable histology (P = .02), Univariate analysis de monstrated that disease stage, tumor histology, and N-myc copy number were also predictive of outcome, Cox regression analysis showed that V I 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 ef fective in the treatment of children with highly vascular, widely diss eminated NB. (C) 1996 by American Society of Clinical Oncology.