Abstract
Objective The antiapoptotic BCL-2 protein has implications for maturation and differentiation
of neural tissue and acts as a strong modulator of carcinogenesis in different tumors.
Recent research focuses not only on its benefit as a prognostic factor, but also as
a potential therapeutic target. The role of BCL-2 in neuroblastoma, the most common
extracranial solid tumor in childhood, remains controversial. The aim of our study
was to determine the gene expression level of BCL-2 in a large cohort of neuroblastoma
patients and its correlation with clinical parameters.
Methods Tumor samples and clinical data were collected from 100 neuroblastoma patients treated
according to the NB2004 protocol of the German Society of Pediatric Oncology and Hematology.
BCL-2 gene expression levels were measured by quantitative reverse transcription polymerase
chain reaction and correlated with clinical parameters.
Results BCL-2 expression was detected in all tumor samples. Relative BCL-2 expression levels
were higher in females versus males (1.839 vs. 1.342; p = 0.0143), in patients with low versus high International Neuroblastoma Staging System
stage (2.051 vs. 1.463; p = 0.0206), in nonmetastatic versus metastatic disease (1.801 vs. 1.342; p = 0.0242), as well as in patients without presurgical chemotherapy (2.145 vs. 1.402;
p = 0.0016), but was not associated with overall survival and MYCN amplification.
Conclusion Our study demonstrates the ubiquitous expression of BCL-2 in neuroblastoma and suggests
the possibility for targeted therapy with BCL-2 inhibitors, even in lower-stage neuroblastoma.
It also underlines the need for further research on concomitant genetic alterations
for a better understanding of the impact of BCL-2 on this pediatric tumor type.
Keywords
neuroblastoma - genetic alterations - BCL-2 - targeted therapy - gene expression
