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American Journal of Pathology, Vol 143, 1543-1550, Copyright © 1993 by American Society for Investigative Pathology

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Expression of the apoptosis-suppressing protein bcl-2, in neuroblastoma is associated with unfavorable histology and N-myc amplification

VP Castle, KP Heidelberger, J Bromberg, X Ou, M Dole and G Nunez
Department of Pediatrics, University of Michigan Medical School, Ann Arbor 48109.

Survival rate in neuroblastoma, a tumor of post-ganglionic sympathetic neuroblasts, correlates with disease stage, tumor histology, and N-myc gene amplification. N-myc amplification is associated with rapid tumor progression and poor survival, but is not present in all cases of poor prognosis neuroblastoma. Moreover, overexpression of N-myc is not sufficient to cause cellular transformation. These data suggest that other genetic factors are important for neuroblastoma development. We investigated the expression of the, bcl-2 proto-oncogene in untreated cases of neuroblastoma. bcl-2 is a novel proto-oncogene that promotes cell growth by inhibiting programmed cell death (apoptosis), a form of cellular demise common during normal neurogenesis. Immunocytochemical localization using a monoclonal anti-bcl-2 antibody revealed that 16 of 40 patient specimens stained positive for bcl-2. bcl-2 was strongly associated with unfavorable histology (P = 0.002) and N-myc gene amplification (P = 0.002) and marginally associated with poor stage disease (P = 0.06). A logistic regression model evaluating the simultaneous association of stage, histology, and N-myc revealed that bcl-2 was most associated with unfavorable histology and N-myc gene amplification. These results support the notion that bcl-2 may play an important role in the genesis or progression of malignant neuroblastoma.

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