Abstract
The molecular mechanisms of adrenocortical carcinoma development are incompletely defined. De-regulation of cellular-to-extracellular matrix interactions and angiogenesis appear among mechanisms associated to the malignant phenotype. Our aim was to investigate, employing PCR-based array profiling, 157 molecules involved in cell-to-matrix interactions and angiogenesis in a frozen series of 6 benign and 6 malignant adrenocortical neoplasms, to identify novel pathogenetic markers. In 14 genes, a significant dysregulation was detected in adrenocortical carcinomas as compared to adenomas, most of them being downregulated. Three exceptions—hyaluronan synthase 1 (HAS-1), laminin α3 and osteopontin genes—demonstrated an increased expression in adrenocortical carcinomas of 4.46, 4.23 and 20.32-fold, respectively, and were validated by immunohistochemistry on a series of paraffin-embedded tissues, including 20 adenomas and 73 carcinomas. Osteopontin protein, absent in all adenomas, was expressed in a carcinoma subset (25/73) (p = 0.0022). Laminin α3 and HAS-1 were mostly expressed in smooth muscle and endothelial cells of the vascular network of both benign and malignant adrenocortical tumors. HAS-1 was also detected in tumor cells, with a more intense pattern in carcinomas. In this group, strong expression was significantly associated with more favorable clinicopathological features. These data demonstrate that cell-to-matrix interactions are specifically altered in adrenocortical carcinoma and identify osteopontin and HAS-1 as novel potential diagnostic and prognostic biomarkers, respectively, in adrenal cortical tumors.
Highlights
Exceptions were represented by three genes which were significantly up-regulated in the Adrenocortical carcinoma (ACC) group
By means of a selective PCR-based gene array approach, we here demonstrated a differential expression of several genes involved in angiogenesis and cell-to-matrix interactions in ACC as compared to adrenal cortical adenomas (ACA)
The present paper showed that ACC is associated to an altered expression of several genes involved in angiogenesis and cell-to-cell/cell-to-matrix interactions, possibly as the result of unbalanced vasculature and neo-angiogenic properties
Summary
Its differential diagnosis from adrenal cortical adenomas (ACA) has been classically based on several pathological and clinical parameters [1]. None of these is per se indicative of malignancy and is most commonly used in combination in a variety of scoring methods, the Weiss system being the most widely employed. Such systems are occasionally challenging to apply and/or time consuming despite several implementations introduced in recent years to provide clinically relevant information [2,3,4]. Complementary to histomorphological evaluation, several markers of malignancy have been reported, including p16, p53, topoisomerase II alpha [5,6,7]
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