Cecília Fernandes Lorea,
Daniel Antunes Moreno,
Kleiton Silva Borges,
Carlos Eduardo Martinelli,
Sonir Roberto Rauber Antonini,
Margaret de Castro,
Silvio Tucci,
Luciano Neder,
Leandra Naira Zambelli Ramalho,
Izilda Cardinalli, Ana Luiza Seidinger,
Maria José Mastellaro,
José Andres Yunes,
Silvia Regina Brandalise,
Luiz Gonzaga Tone,
Carlos Alberto Scrideli
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ABSTRACT: 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.
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.
A significant association was observed between tumor size ≥100 g and lower expression levels of the BCL2 (P=0.03) and TNF (P=0.05) genes; between stage IV and lower expression levels of CASP3 (P=0.008), CASP9 (P=0.02), BCL2 (P=0.002), TNF (P=0.05), and NFKB (P=0.03); Weiss score ≥3 and lower expression of TNF (P=0.01); unfavorable event and higher expression values of CASP9 (P=0.01) and lower values of TNF (P=0.02); and death and lower expression of BCL2 (P=0.04). 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.
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.
European Journal of Endocrinology 05/2012; 167(2):199-208. · 3.42 Impact Factor
