Impact of BCL-2 Expression on Course of Disease in Neuroblastoma

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.