Metastatic pheochromocytoma and paraganglioma: Somatostatin receptor 2 expression, genetics and therapeutic responses

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

  • Alessa Fischer - , Universitätsspital Zürich (Autor:in)
  • Simon Kloos - , Universitätsspital Zürich (Autor:in)
  • Umberto Maccio - , Universitätsspital Zürich (Autor:in)
  • Juliane Friemel - , Universitätsspital Zürich (Autor:in)
  • Hanna Remde - , Hospital de Basurto (Autor:in)
  • Martin Fassnacht - , Hospital de Basurto (Autor:in)
  • Christina Pamporaki - , Zentrum für Informationsdienste und Hochleistungsrechnen (ZIH), Medizinische Klinik und Poliklinik III, Universitätsklinikum Carl Gustav Carus Dresden (Autor:in)
  • Graeme Eisenhofer - , Medizinische Klinik und Poliklinik III, Universitätsklinikum Carl Gustav Carus Dresden (Autor:in)
  • Henri J L M Timmers - , Radboud University Medical Center (Autor:in)
  • Mercedes Robledo - , Hereditary Endocrine Cancer Group. Spanish National Cancer Research Center (CNIO) (Autor:in)
  • Stephanie M J Fliedner - , Universitätsklinikum Schleswig-Holstein Campus Lübeck (Autor:in)
  • Katharina Wang - , Hospital de Basurto (Autor:in)
  • Julian Maurer - , Hospital de Basurto (Autor:in)
  • Astrid Reul - , Universitätsspital Zürich (Autor:in)
  • Kathrin Zitzmann - , Hospital de Basurto (Autor:in)
  • Nicole Bechmann - , Institut für Klinische Chemie und Laboratoriumsmedizin, Universitätsklinikum Carl Gustav Carus Dresden (Autor:in)
  • Gintarė Žygienė - , Institut für Klinische Chemie und Laboratoriumsmedizin (Autor:in)
  • Susan Richter - , Institut für Klinische Chemie und Laboratoriumsmedizin, Universitätsklinikum Carl Gustav Carus Dresden (Autor:in)
  • Constanze Hantel - , Medizinische Klinik und Poliklinik III, Endokrinologikum Hamburg, Universitätsspital Zürich, Universitätsklinikum Carl Gustav Carus Dresden (Autor:in)
  • Diana Vetter - , Hospital de Basurto (Autor:in)
  • Kuno Lehmann - , Hospital de Basurto (Autor:in)
  • Hermine Mohr - , Universitätsklinikum Carl Gustav Carus Dresden (Autor:in)
  • Natalia S Pellegata - , Universitätsklinikum Carl Gustav Carus Dresden (Autor:in)
  • Martin Ullrich - , Fakultät Chemie u. Lebensmittelchemie, Helmholtz-Zentrum Dresden-Rossendorf (Autor:in)
  • Jens Pietzsch - , Helmholtz-Zentrum Dresden-Rossendorf (Autor:in)
  • Christian G Ziegler - , Medizinische Klinik und Poliklinik III, Hochschulmedizin (Medizinische Fakultät und Universitätsklinikum), Technische Universität Dresden, Universitätsklinikum Carl Gustav Carus Dresden (Autor:in)
  • Stefan R Bornstein - , Medizinische Klinik und Poliklinik III, Endokrinologikum Hamburg, Universitätsspital Zürich, Universitätsklinikum Carl Gustav Carus Dresden (Autor:in)
  • Matthias Kroiss - , Hospital de Basurto (Autor:in)
  • Martin Reincke - , Hospital de Basurto (Autor:in)
  • Karel Pacak - , Eunice Kennedy Shriver NICHD (Autor:in)
  • Ashley B Grossman - , University of Oxford (Autor:in)
  • Felix Beuschlein - , Universitätsspital Zürich (Autor:in)
  • Svenja Nölting - , Universitätsspital Zürich (Autor:in)

Abstract

CONTEXT: Pheochromocytomas/paragangliomas (PPGLs) with pathogenic mutations in the succinate dehydrogenase subunit B (SDHB) are associated with a high metastatic risk. Somatostatin receptor 2 (SSTR2)-dependent imaging is the most sensitive imaging modality for SDHB-related PPGLs, suggesting that SSTR2 expression is a significant cell surface therapeutic biomarker of such tumors.

OBJECTIVE: Exploration of the relationship between SSTR2 immunoreactivity and SDHB immunoreactivity, mutational status, and clinical behavior of PPGLs. Evaluation of SSTR-based therapies in metastatic PPGLs.

DESIGN: Retrospective analysis of a multicenter cohort of PPGLs.

SETTING: Six specialized Endocrine Tumor Centers in Germany, the Netherlands and Switzerland.

PATIENTS: Patients with PPGLs participating in the ENSAT registry.

METHODS: Clinical data were extracted from medical records and immunohistochemistry (IHC) for SDHB and SSTR2 was performed in patients with available tumor tissue. Immunoreactivity of SSTR2 was investigated using Volante scores.

MAIN OUTCOME MEASURE: Association of SSTR2 IHC positivity with genetic and clinic-pathological features of PPGLs.

RESULTS: Of 202 patients with PPGLs, 50% were SSTR2 positive. SSTR2 positivity was significantly associated with SDHB- and SDHx-related PPGLs, with the strongest SSTR2 staining intensity in SDHB-related PPGLs (p = 0.01). Moreover, SSTR2 expression was significantly associated with metastatic disease independent of SDHB/SDHx mutation status (p < 0.001).In metastatic PPGLs, the disease control rate with first-line SSTR-based radionuclide therapy was 67% (n = 22, n = 11 SDHx), and with first-line "cold" somatostatin analogs 100% (n = 6, n = 3 SDHx).

CONCLUSIONS: SSTR2 expression was independently associated with SDHB/SDHx mutations and metastatic disease. We confirm a high disease control rate of somatostatin receptor-based therapies in metastatic PPGLs.

Details

OriginalspracheEnglisch
Seiten (von - bis)2676-2685
Seitenumfang10
FachzeitschriftThe Journal of clinical endocrinology and metabolism
Jahrgang108(2023)
Ausgabenummer10
Frühes Online-Datum22 März 2023
PublikationsstatusVeröffentlicht - 22 März 2023
Peer-Review-StatusJa

Externe IDs

WOS 000973335200001
unpaywall 10.1210/clinem/dgad166
ORCID /0000-0002-6932-333X/work/142239677
ORCID /0000-0002-3549-2477/work/142244905
Mendeley ac998be4-5a02-3ca8-b7e5-fdbd9fce240e
Scopus 85176224180

Schlagworte

Forschungsprofillinien der TU Dresden

Ziele für nachhaltige Entwicklung

Schlagwörter

  • Adrenal Gland Neoplasms/genetics, Humans, Metastatic pheochromocytoma, Neoplasms, Second Primary, Paraganglioma, Paraganglioma/genetics, Pheochromocytoma/genetics, Prrt, Receptors, Somatostatin/genetics, Retrospective Studies, SDHB mutation, SDHx mutation, Somatostatin receptor 2, Somatostatin receptor-based therapies, Succinate Dehydrogenase/genetics, PRRT, metastatic pheochromocytoma/paraganglioma, somatostatin receptor-based therapies, somatostatin receptor 2

Bibliotheksschlagworte