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-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.
Castle
V P
VP
Department of Pediatrics, University of Michigan Medical School, Ann Arbor 48109.
Heidelberger
K P
KP
Bromberg
J
J
Ou
X
X
Dole
M
M
Nuñez
G
G
D000293:Adolescent; D017209:Apoptosis / Q000502:physiology*; D015153:Blotting, Western; D002471:Cell Transformation, Neoplastic / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D016259:Genes, myc / Q000235:genetics*; D006801:Humans; D007124:Immunoenzyme Techniques; D007223:Infant; D007231:Infant, Newborn; D009367:Neoplasm Staging; D009447:Neuroblastoma / Q000737:chemistry / Q000235:genetics* / Q000473:pathology*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000032:analysis* / Q000235:genetics / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2