EXPRESSION OF THE APOPTOSIS-SUPPRESSING PROTEIN BCL-2, IN NEUROBLASTOMA IS ASSOCIATED WITH UNFAVORABLE HISTOLOGY AND N-MYC AMPLIFICATION

Survival rate in neuroblastoma, a tumor of post-ganglionic sympathetic neuroblasts, correlates with disease stage, tumor histology, and N-my c gene amplification. N-myc amplification is associated with rapid tum or progression and poor survival, but is not present in all cases of p oor prognosis neuroblastoma Moreover, overexpression of N-myc is not s ufficient to cause cellular transformation. These data suggest that ot her genetic factors are important for neuro-blastoma development. We i nvestigated the expression ofthe, bc1-2 proto-oncogene in untreated ca ses of neuroblastoma. bc1-2 is a novel protooncogene that promotes cel l growth by inhibiting programmed cell death (apoptosis), a form of ce llular demise common during normal neurogenesis. Immunocytochemical lo calization using a monoclonal anti-bc1-2 antibody revealed that 16 of 40 patient specimens stained positive for bc1-2. bc1-2 was strongly as sociated with unfavorable histology (P = 0.002) and N-myc gene amplifi cation (P = 0.002) and marginally associated with poor stage disease ( P = 0.06). A logistic regression model evaluating the simultaneous ass ociation of stage, histology, and N-myc revealed that bc1-2 was most a ssociated with unfavorable histology and N-myc gene amplification. The se results support the notion that bc1-2 may play an important role in the genesis or progression of malignant neuroblastoma.