Biochemical evidence for a mature phenotype in morphologically poorly differentiated neuroblastomas with a favourable outcome

• Published in: European journal of cancer (1990) Vol. 31; no. 4; pp. 435 - 443
• Main Authors: Hedborg, F., Bjelfman, C., Sparén, P., Sandstedt, B., Påhlman, S.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 1995
• Subjects: age; Age Factors; Biomarkers, Tumor - metabolism; Cell Differentiation; Child; Child, Preschool; csrc; Follow-Up Studies; histological grade; Humans; Infant; Infant, Newborn; Medicin och hälsovetenskap; MYCN amplification; neuroblastoma; Neuroblastoma - metabolism; Neuroblastoma - pathology; NSE; Phenotype; Phosphopyruvate Hydratase - metabolism; Prognosis; Proto-Oncogene Proteins pp60(c-src) - metabolism; stage; Survival Rate; synaptophysin; Synaptophysin - metabolism; Tumor Cells, Cultured; tumour site; histological grade; synaptophysin; NSE; stage; tumour site; neuroblastoma; MYCN amplification; prognosis; age; csrc
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/0959-8049(95)00025-E

Neuroblastoma is an embryonal tumour of the sympathetic nervous system with marked heterogeneity in terms of histological maturity and clinical course. A previous study revealed that high tumour levels of the csrc protein, particularly its neuronal isoform (pp60
csrcN), correlated with favourable outcome. To test whether this feature reflects a higher degree of neuronal maturation in these tumours, an extended series (47 consecutive neuroblastomas and 10 ganglioneuromas) were analysed for levels of csrc protein isoforms, neuron-specific enolase, and synaptophysin. Immunoblotting and radioimmunoassay techniques were employed. The results were compared with conventional histological signs of neuronal maturation. High pp60
csrcN levels were specific for prognostically favourable neuroblastomas and correlated with high neuronal marker levels. However, signs of histological maturation correlated poorly with these parameters. It is therefore concluded that low stage tumours are highly differentiated in biochemical terms despite their frequently immature histology. Furthermore, the clinical usefulness of these biochemical parameters as prognostic markers was compared with established parameters in a multivariate analysis. Stage 4 disease,
MYCN amplification, and age above 18 months at diagnosis was the most powerful combination of variables found for predicting a poor outcome. As expected, none of the neuronal differentiation markers investigated could add to the prediction of aggressive disease when compared with this model. However, high expression of pp60
csrcN appeared to be useful in predicting long-term survival in high stage infant neuroblastoma.