Abstract
Several unique features of neuroblastoma (NB), including the capacity for spontaneous regression and maturation to benign pathology, suggest that genes that regulate cellular proliferation, survival and differentiation may be involved in directing clinical tumour aggressiveness. The in situ expression of Bcl-2, Rb, p21, p53 and Bax proteins, as well as the proliferation marker proliferating cell nuclear antigen (PCNA) were examined immunocytochemically in a selection of 38 stage- and outcome-identified NB tumours. Apoptotic cells were identified morphologically and by a DNA fragmentation labelling technique (TUNEL). Although the tumour cell density of Bcl-2, p53, Bax, PCNA and TUNEL positivity correlated with patient survival, a spatially organized expression pattern was further recognized in stroma-poor differentiating tumours. Immature tumour cells adjacent to thin fibrovascular stroma are proliferating, as evidenced by PCNA positivity, and often express Bcl-2. At increasing distance from this fibrovascular stroma, intermediately differentiated tumour cells express Rb, while with more advanced differentiation, proliferation ceases and Bcl-2 immunoreactivity is lost. The most differentiated tumour cells, which often express p53, and occasionally p21 and Bax, lie adjacent to TUNEL-positive, morphologically apoptotic cells. This spatial organization in favourable outcome NB tumours suggests that physiological regulation of differentiation and apoptosis may be involved in tumour regression.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 24 print issues and online access
$259.00 per year
only $10.79 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Hoehner, J., Gestblom, C., Olsen, L. et al. Spatial association of apoptosis-related gene expression and cellular death in clinical neuroblastoma. Br J Cancer 75, 1185–1194 (1997). https://doi.org/10.1038/bjc.1997.203
Issue Date:
DOI: https://doi.org/10.1038/bjc.1997.203
This article is cited by
-
Calreticulin Regulates VEGF-A in Neuroblastoma Cells
Molecular Neurobiology (2015)
-
Spontaneous regression of colorectal cancer: a review of cases from 1900 to 2005
International Journal of Colorectal Disease (2007)
-
Spontaneous regression in recurrent epithelial ovarian cancer
Archives of Gynecology and Obstetrics (2007)
-
Antisense bcl-2 transfection up-regulates anti-apoptotic and anti-oxidant thioredoxin in neuroblastoma cells
Journal of Neuro-Oncology (2005)
-
ID2 expression in neuroblastoma does not correlate to MYCN levels and lacks prognostic value
Oncogene (2003)