Endocrine Abstracts (2008) 16 P291

Differences in the gene expression patterns of several immune related genes in various human adrenocortical tumors

Peter Szabó1, Zoltán Wiener2, Zsófia Tömböl1, Gergely Tölgyesi2, Katalin Kövesdi1, Roland Farkas1, János Horányi3, Rolf C Gaillard4, András Falus2, Károly Rácz1 & Peter Igaz1

12nd Department of Medicine, Semmelweis University, Budapest, Hungary; 2Department of Genetics, Cell- and Immunobiology, Semmelweis University, Budapest, Hungary; 31st Department of Surgery, Semmelweis University, Budapest, Hungary; 4Department of Endocrinology, Diabetology and Metabolism, University Hospital, Lausanne, Switzerland.

Introduction: The adrenal cortex is highly involved at the immune-neuroendocrine interface, and several cytokines are known to influence the proliferation, differentiation, apoptosis and hormone production of adrenocortical cells. We therefore hypothesized that immune mediators might be involved in adrenal tumorigenesis, as well. Gene expression patterns of various inflammatory and immune mediators were studied by a functional genomics/bioinformatics approach.

Methods: Hormonally inactive, cortisol-, aldosterone-secreting benign and malignant adrenocortical tumors, and normal adrenocortical tissues were studied by microarray analysis. Both 8×1.5 K custom microarrays focusing on immune-related genes and whole genome 4×44 K microarrays were performed in 6–10 samples in each group. Real-time RT-PCR and western-blotting were used for the validation of results.

Results: Seventy genes showed significant (P<0.05, min. 2–2.5 fold) differences among different groups by microarray analysis. Among these, toll like receptor 4 (TLR4), macrophage migration inhibitory factor (MIF), fibroblast growth factor 11 (FGF11), fibroblast growth factor receptor 1 (FGFR1), interleukin 17 (IL-17) and IL-17 receptor beta (IL-17RB) expression levels were validated. TLR4 expression was highest in normal tissues and hormonally inactive tumors, while low expression levels were measured in the other groups. MIF and FGF11 expression levels were characteristically high in hormonally inactive tumors, whereas barely detectable in the other groups. In contrast, FGFR1 was highest in normal tissues, low expression was found in tumors. IL-17 expression was not significantly different, whereas IL-17RB expression was significantly reduced in inactive tumors.

Discussion: Our findings underline the possibility that some immune related genes may be involved in the pathogenesis of adrenocortical tumors.