Cytoplasmic HIF-2α as tissue biomarker to identify metastatic sympathetic paraganglioma
(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.
(Less)
- author
- organization
- publishing date
- 2023
- 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}}, }