Evaluation of somatostatin, CXCR4 chemokine and endothelin A receptor expression in a large set of paragangliomas
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Daniel Kaemmerer1, Jörg Sänger2, Ruza Arsenic3, Jan G. D’Haese4, Jens Neumann5, Annette Schmitt-Graeff6, Ralph Markus Wirtz7, Stefan Schulz8 and Amelie Lupp8
1Department of General and Visceral Surgery, Zentralklinik Bad Berka, Bad Berka, Germany
2Laboratory of Pathology and Cytology Bad Berka, Bad Berka, Germany
3Institute of Pathology, Charité University Hospital Berlin, Berlin, Germany
4Department of General, Visceral, Transplantation, Vascular and Thoracic Surgery, Hospital of the University of Munich, Munich, Germany
5Department of Pathology, Ludwig-Maximilians-University Munich, Munich, Germany
6Department of Pathology, Albert-Ludwigs-University of Freiburg, Freiburg, Germany
7STRATIFYER Molecular Pathology GmbH, Köln, Germany
8Institute of Pharmacology and Toxicology, Jena University Hospital, Jena, Germany
Amelie Lupp, email: [email protected]
Keywords: somatostatin receptors, CXCR4, endothelin receptor A, immunohistochemistry, paraganglioma
Abbreviations: Ct, cycle threshold; ETA, endothelin receptor A; IHC, immunohistochemistry; SST, somatostatin receptor
Received: June 07, 2017 Accepted: August 17, 2017 Published: September 23, 2017
Paragangliomas are predominantly benign tumors, but in some cases invasive growth and also metastasis are observed. Given the limited number of nonsurgical treatment options, novel target structures for diagnostics and therapy of this tumor entity are urgently needed.
In the present study, expression of all five somatostatin receptor (SST) subtypes, chemokine receptor CXCR4 and endothelin receptor type A (ETA) was assessed by means of immunohistochemistry in a total of 66 paraffin-embedded paraganglioma samples from 55 patients. The stainings were rated by means of the Immunoreactive Score and correlated to clinical data and to succinate dehydrogenase subunit B (SDHB) expression.
SST2A was by far the most prominent receptor in the paragangliomas investigated. It was present in 89% of the tumors at a high intensity, followed by SST5, SST3, SST1 and SST4, which were detected in 47%, 35%, 35% and 13% of the samples, respectively. SDHB positive tumors exhibited significantly higher SST2A and SST3 expression as compared to SDHB negative cases. There was no correlation between SST and Ki-67 expression or grading of the tumors and no difference in SST expression between primary tumors and metastases. Cell surface expression of CXCR4 and ETA was detected only in few samples. On tumor capillaries, however, exceptionally strong staining for these two receptors was noticed in the vast majority of the tumors.
In conclusion, paragangliomas are well suited for SST2A-based diagnostics and treatment modalities. An indirect targeting of these highly vascularized tumors via CXCR4 or ETA may also represent a promising future strategy.
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