Cytoplasmic HIF-2α As Tissue Biomarker to Identify Metastatic Sympathetic Paraganglioma

Overview

Journal Sci Rep

Specialty Science

Date 2023 Jul 18

PMID 37463949

Authors

Sinan Karakaya

Lisa Gunnesson

Erik Elias

Paula Martos-Salvo

Mercedes Robledo

Ola Nilsson

Bo Wangberg

Frida Abel

Sven Pahlman

Andreas Muth

Sofie Mohlin

Affiliations

Soon will be listed here.

Abstract

Pheochromocytomas (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.

Citing Articles

PD-L1 and HIF-2α Upregulation in Head and Neck Paragangliomas after Embolization.

Fischer A, Maccio U, Wang K, Friemel J, Broglie Daeppen M, Vetter D Cancers (Basel). 2023; 15(21).

PMID: 37958373 PMC: 10650267. DOI: 10.3390/cancers15215199.

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