Endocrine Abstracts

Background: Pheochromocytoma (Pheo) is a tumor deriving from chromaffin cells. It can be studied using ¹⁸F-dihydroxyphenylalanine (DOPA) - positron emission tomography (PET) due to its overexpression of L-type amino acid transporters (LAT1 and LAT2). The oncogenic pathways involved are still poorly understood. This study examined the relationship between ¹⁸F-DOPA-PET uptake and LAT1 expression, and explored the role of miR-375 and putative target genes.

Methods: A consecutive series of 58 Pheo were retrospectively analyzed, performing ¹⁸F-DOPA-PET in 32/58 patients. qRT-PCR was used to assess the expression of LAT1, LAT2, phenylethanolamine N-methyltransferase (PNMT), miR-375, and the major components of the Hippo and Wnt pathways. 24 h-urinary metanephrine, normetanephrine, epinephrine and norepinephrine were analyzed for diagnostic purposes prior to surgery. Principal germline mutations associated with hereditary Pheo were also studied.

Results: Pheo tissues had significantly higher LAT1, LAT2 and PNMT mRNA levels than normal adrenal tissues. MiR-375 was strongly overexpressed. YAP1 and TNKS1 were upregulated, while beta-catenin, axin2 and MCT8 were downregulated. A positive relationship was found between ¹⁸F-DOPA-PET SUVmean and LAT1 gene expression, as was for 24 h-urinary norepinephrine and LAT1.

Conclusion: The present study confirms in a larger population that LAT1 and LAT2 are upregulated in Pheo. It provides the first experimental proof of a quantitative correlation between ¹⁸F-DOPA uptake and LAT1 expression levels, and the first evidence of miR-375 overexpression in Pheo, with a consensual downregulation of the Wnt signaling. The present report also pave the way to studies on the Hippo pathway as a possible new oncogenic driver in Pheo