Expression profile of apoptosis-related genes in childhood adrenocortical tumors: low level of expression of BCL2 and TNF genes suggests a poor prognosis

Background: Impaired apoptosis has been implicated in the development of childhood adrenocortical tumors (ACT), although the expression of apoptosis-related gene expression in such tumors has not been reported. Methods: The mRNA expression levels of the genes CASP3, CASP8, CASP9, FAS , TNF, NFKB, and BCL2 were analyzed by quantitative real-time PCR in consecutive tumor samples obtained at diagnosis from 60 children with a diagnosis of ACT and in 11 non-neoplastic adrenal samples. BCL2 and TNF protein expression was analyzed by immunohistochemistry. Results: A significant association was observed between tumor size R100 g and lower expression levels of the BCL2 (PZ0.03) and TNF (PZ0.05) genes; between stage IV and lower expression levels of CASP3 (PZ0.008), CASP9 (PZ0.02), BCL2 (PZ0.002), TNF (PZ0.05), and NFKB (PZ0.03); Weiss score R3 and lower expression of TNF (PZ0.01); unfavorable event and higher expression values of CASP9 (PZ0.01) and lower values of TNF (PZ0.02); and death and lower expression of BCL2 (PZ0.04). Underexpression of TNF was associated with lower event-free survival in uni- and multivariate analyses (P!0.01). Similar results were observed when patients with Weiss score !3 were excluded. Conclusion: This study supports the participation of apoptosis-related genes in the biology and prognosis of childhood ACT and suggests the complex role of these genes in the pathogenesis of this tumor.