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. 2021 May 6;11(5):378.
doi: 10.3390/jpm11050378.

Differential Expression Profiles of Cell-to-Matrix-Related Molecules in Adrenal Cortical Tumors: Diagnostic and Prognostic Implications

Marco Volante  1 , Ida Rapa  1 , Jasna Metovic  2 , Francesca Napoli  1 , Cristian Tampieri  3 , Eleonora Duregon  1 , Massimo Terzolo  4 , Mauro Papotti  2
Affiliations

Differential Expression Profiles of Cell-to-Matrix-Related Molecules in Adrenal Cortical Tumors: Diagnostic and Prognostic Implications

Marco Volante et al. J Pers Med. .

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.

Keywords: adrenal cortex; angiogenesis; carcinoma; gene expression; hyaluronan synthase 1; osteopontin.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Osteopontin expression in adrenocortical carcinoma. The pattern of staining in adrenocortical carcinoma tumor cells is cytoplasmic, either with a peculiar dot-like paranuclear appearance (a) or diffuse within the cytoplasm (b). The intratumoral lymphocytes (b, bottom left) are un-reactive (original magnification 400×).
Figure 2
Figure 2
Laminin α3 immunoexpression is restricted to the vascular network of both an adrenocortical adenoma with rare and thin vessels (a, 100×) and an adrenocortical carcinoma containing numerous small and medium size vessels (b, 100×). Hyaluronan synthase-1 is also strongly expressed by smooth muscle cells of vessel walls in both adrenocortical adenoma (c, 100×) and carcinoma (d inset, 200×). In addition, tumor cells of adenomas present more frequently a negative or weakly positive pattern of staining (c, 100×), while carcinoma cells may show a strong cytoplasmic reactivity (d, 100×).
Figure 3
Figure 3
Univariate disease free (a) and overall (b) survival analysis in HAS-1 tumor cell positive and negative adrenocortical carcinomas.
See this image and copyright information in PMC

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