Study of proliferation and apoptosis in neuroblastoma. Their relation with other prognostic factors.
BACKGROUND
Our objective was to study the proliferation and apoptotic process in 111 cases of neuroblastoma (NB) and to seek their relationship with other prognostic factors and survival.


METHODS
Immunohistochemistry following ABC peroxidase was carried out for PCNA, Ki-67, bcl-2, and p53 proteins. Apoptosis analysis was performed with in situ detection of chromosomal breakdown. Molecular detection of DNA ladders by electrophoresis and amplification of MYCN was studied with PCR and Southern blot. Statistical study was performed with Pearson chi(2) and Kruskal-Wallis tests and Cox regression.


RESULTS
Our results indicate that proliferative factors PCNA and Ki-67 were correlated to each other as well as to advanced stage and MYCN amplification. Regarding apoptosis, we found expression of bcl-2 protein in cases of NB without differentiation and advanced stages. p53 protein showed an inverse relation with bcl-2 and cell death measured by assay protein. In situ determination of apoptosis was found mainly in differentiated and stage 4s cases. Multivariate analysis revealed protein as the most independent risk factor of our study.


CONCLUSIONS
The study of cellular proliferation and apoptosis contributes with information of prognostic value that could be applied to the design of different protocols for treatment of neuroblastoma.
del Carmen Mejía
Ma
M
Departamento de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México (UNAM), Mexico City, Mexico. maria.c.mejia@uv.es
Navarro
Samuel
S
Pellín
Antonio
A
Ruíz
Amparo
A
Castel
Victoria
V
Llombart-Bosch
Antonio
A
D017209:Apoptosis; D015139:Blotting, Southern; D002454:Cell Differentiation; D002455:Cell Division; D002648:Child; D002675:Child, Preschool; D004247:DNA / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007231:Infant, Newborn; D019394:Ki-67 Antigen / Q000096:biosynthesis; D008297:Male; D008938:Mitosis; D015999:Multivariate Analysis; D009447:Neuroblastoma / Q000175:diagnosis / Q000401:mortality / Q000473:pathology*; D016133:Polymerase Chain Reaction; D011379:Prognosis; D018809:Proliferating Cell Nuclear Antigen / Q000096:biosynthesis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis
D019394:Ki-67 Antigen; D018809:Proliferating Cell Nuclear Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D004247:DNA