ABSTRACT
Adrenocortical cancer is a rare tumor and its prognosis is poor. Although numerous tumor-associated genetic and signal transduction alterations have been described to date, its pathogenesis is still unclear. Hybridization-based DNA microarray approaches may reveal significant gene expression alterations and may thus contribute to a better understanding of tumorigenesis and may identify molecular markers applicable for the distinction of benign and malignant lesions. Beside gene expression patterns, studies on microRNAs seem to be useful, as well. Novel therapeutical targets might be established by these approaches. In this review, the authors attempt to summarize the main findings of mRNA and microRNA expression microarray studies performed to date in adrenocortical cancer including a recent meta-analysis of gene expression data and present novel pathogenic pathways.
ABSTRACT
Adrenocortical cancer is a rare tumor with poor prognosis. Whereas most cases occur in a sporadic setting, there are very rare hereditary forms that are important for the understanding of tumor pathogenesis. The hereditary syndromes associated with adrenocortical cancer are: Li-Fraumeni's syndrome, Beckwith-Wiedemann's syndrome and familial adenomatous polyposis, whereas multiple endocrine neoplasia type 1, Carney's complex and McCune-Albright's syndrome mostly predispose to benign adrenocortical tumors. Overexpression of insulin like growth factor 2, activation of Wnt/beta-catenin and cAMP-protein kinase A signaling, as well as mutations of p53 and MEN1 genes are regarded as major pathogenetic mechanisms. Options for medical treatment of adrenocortical cancer are rather limited. Recently published molecular-bioinformatical studies have revealed several previously unknown pathogenetic pathways that may even represent potential drug targets. In this study, the pathogenesis of hereditary tumor syndromes, the alterations in sporadic tumors and the most recent molecular-bioinformatical observations are discussed.
