Transcriptional profiling enables molecular classification of adrenocortical tumours

Objective: Tumours in the adrenocortex are common human tumours. Malignancy, is however. rare, the yearly incidence being 0.5-2 per million inhabitants. but associated with a very aggressive behaviour, Adrenocortical tumours are often associated with altered hormone production with it variety of clinical symptoms. The aggressiveness of carcinomas together with the high frequency of adenomas calls for it deeper understanding of the Underlying biological mechanisms and all improvement of the diagnostic possibilities. Methods: Microarray gene expression analysis was performed in tumours of adrenocortex with emphasis on malignancy as well as hormonal activity. The sample set consisted of 17 adenomas, 11 carcinomas and 4 histological normal adrenocortexes. RNA from these was hybridised according to it reference design on microarrays harbouring 29 760 human cDNA clones. Confirmation was performed with quantitative real time-PCR and western blot analysis. Results: Unsupervised Clustering to reveal relationships between samples based oil the entire gene expression profile resulted in two subclusters: carcinomas and non-cancer specimens. A large number of genes were accordingly found to be differentially expressed comparing carcinomas to adenomas. Among these were IGF2, FGFR1 and FGFR4 in growth factor signalling the most predominant and also the USP4, UBE2C and UFD1L in the ubiquitin-proteasome pathway. Moreover, two subgroups of carcinomas were identified with different survival outcome, suggesting that survival prediction can be made oil the basis of gene expression profiles. Regarding adenomas with aldosterone over production. OSBP and VEGFB were among the most up-regulated genes compared with the other samples. Conclusions: Adrenocortical carcinomas are associated with a distinct molecular signature apparent ill their gene expression profiles. Differentially expressed genes were identified associated with malignancy, survival as well as hormonal activity providing it resource of candidate genes for all exploration of possible drug targets and diagnostic and prognostic markers.