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.

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Three large U.S. epidemiological surveys researching the prevalence of comorbid psychiatric illness and "substance abuse disorders" are reviewed: the Epidemiological Catchment Area Study, (N=20,219); the National Comorbidity Survey (N=8098), and the National Longitudinal Alcohol Epidemiological Survey (N=42,862). Findings suggest that comorbidity is highly prevalent but that longitudinal information remains limited limited--which restricts understanding of its "natural history," stability, common risk factors, and causal relationships.

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