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

Karakaya, Sinan LU ; Gunnesson, Lisa ; Elias, Erik ; Martos-Salvo, Paula LU ; Robledo, Mercedes ; Nilsson, Ola ; Wängberg, Bo ; Abel, Frida ; Påhlman, Sven LU and Muth, Andreas , et al. (2023) In Scientific Reports 13(1).
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... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Scientific Reports
volume
13
issue
1
article number
11588
publisher
Nature Publishing Group
external identifiers
  • pmid:37463949
  • scopus:85165240059
ISSN
2045-2322
DOI
10.1038/s41598-023-38606-8
language
English
LU publication?
yes
id
372b2074-0626-4384-a76b-ddf6e3bcbfd7
date added to LUP
2023-08-29 15:21:13
date last changed
2024-04-20 02:10:02
@article{372b2074-0626-4384-a76b-ddf6e3bcbfd7,
  abstract     = {{<p>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.</p>}},
  author       = {{Karakaya, Sinan and Gunnesson, Lisa and Elias, Erik and Martos-Salvo, Paula and Robledo, Mercedes and Nilsson, Ola and Wängberg, Bo and Abel, Frida and Påhlman, Sven and Muth, Andreas and Mohlin, Sofie}},
  issn         = {{2045-2322}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Scientific Reports}},
  title        = {{Cytoplasmic HIF-2α as tissue biomarker to identify metastatic sympathetic paraganglioma}},
  url          = {{http://dx.doi.org/10.1038/s41598-023-38606-8}},
  doi          = {{10.1038/s41598-023-38606-8}},
  volume       = {{13}},
  year         = {{2023}},
}