Cytoplasmic HIF-2α as tissue biomarker to identify metastatic sympathetic paraganglioma

Author:

Karakaya Sinan,Gunnesson Lisa,Elias Erik,Martos-Salvo Paula,Robledo Mercedes,Nilsson Ola,Wängberg Bo,Abel Frida,Påhlman Sven,Muth Andreas,Mohlin Sofie

Abstract

AbstractPheochromocytomas (PCCs) and paragangliomas (PGLs) are rare neuroendocrine tumors. PGLs can further be divided into sympathetic (sPGLs) and head-and-neck (HN-PGLs). There are virtually no treatment options, and no cure, for metastatic PCCs and PGLs (PPGLs). Here, we composed a tissue microarray (TMA) consisting of 149 PPGLs, reflecting clinical features, presenting as a useful resource. Mutations in the pseudohypoxic marker HIF-2α correlate to an aggressive tumor phenotype. We show that HIF-2α localized to the cytoplasm in PPGLs. This subcompartmentalized protein expression differed between tumor subtypes, and strongly correlated to proliferation. Half of all sPGLs were metastatic at time of diagnosis. Cytoplasmic HIF-2α was strongly expressed in metastatic sPGLs and predicted poor outcome in this subgroup. We propose that higher cytoplasmic HIF-2α expression could serve as a useful clinical marker to differentiate paragangliomas from pheochromocytomas, and may help predict outcome in sPGL patients.

Funder

Lund University

Publisher

Springer Science and Business Media LLC

Subject

Multidisciplinary

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