Cristóbal Bernardo-Castiñeira1, Inés Sáenz-de-Santa-María1, Nuria Valdés2, Aurora Astudillo3, Milagros Balbín4, Ana S Pitiot4, Paula Jiménez-Fonseca5, Bartolomé Scola6, Isabel Tena7, María-José Molina-Garrido8, María-Agustina Sevilla9, Elena Beristein10, Lluís Forga11, Carles Villabona12, Josep Oriola13, Irene Halperin13, Carlos Suarez14, María-Dolores Chiara1. 1. Institute of Sanitary Research of Asturias, Institute of Oncology of Asturias (IUOPA), CIBERONC, Hospital Central de Asturias, Universidad de Oviedo, Oviedo, Spain. 2. Service of Endocrinology and Nutrition, Hospital Central de Asturias, Oviedo, Spain. 3. Service of Pathology, Hospital Central de Asturias, Oviedo, Spain. 4. Service of Molecular Oncology, Hospital Central de Asturias, Oviedo, Spain. 5. Service of Medical Oncology, Hospital Central de Asturias, Oviedo, Spain. 6. Service of Otorhinolaryngology, Hospital Gregorio Marañón, Madrid, Spain. 7. Service of Medical Oncology, Hospital Provincial de Castellón, Castellón, Spain. 8. Service of Medical Oncology, Hospital General Virgen de la Luz, Cuenca, Spain. 9. Service of Otorhinolaryngology, Hospital Virgen del Rocío, Sevilla, Spain. 10. Laboratory of Molecular Genetic, Hospital Universitario Araba-Txagorritxu, Vitoria-Gasteiz, Spain. 11. Service of Endocrinology and Nutrition, Complejo Hospitalario de Navarra, Pamplona, Spain. 12. Service of Endocrinology and Nutrition, Hospital Universitario de Bellvitge, Barcelona, Spain. 13. Laboratory of Biochemistry and Molecular Genetics and Endocrinology and Nutrition Service, Hospital Clinic, Barcelona, Spain. 14. Service of Otorhinolaryngology, Hospital Central de Asturias, Oviedo, Spain.
Abstract
BACKGROUND: Succinate dehydrogenase subunit B (SDHB) immunohistochemistry was considered a valuable tool to identify patients with inherited paraganglioma/pheochromocytoma (PGL/PCC). However, previous studies jointly analyzed 2 related but clinically distinct entities, parasympathetic head and neck paragangliomas (HNPGLs) and sympathetic PCCs/PGLs. Additionally, a role for hypoxia inducible factor-1α (HIF-1α) as a biomarker for succinate dehydrogenase (SDHx)-mutated tumors has not been studied. Here, we evaluated the utility of SDHB/HIF-1α proteins in HNPGLs and PCCs/PGLs as clinically useful biomarkers. METHODS: The SDHB/succinate dehydrogenase subunit A (SDHA)/HIF-1α immunohistochemistry analysis was performed in 158 genetically defined patients. RESULTS: Similarly to PCCs/PGLs, SDHB immune-negativity correlated with SDHx-mutations in HNPGLs (P < .0001). The HIF-1α stabilization was associated with SDHx-mutations in HNPGLs (P = .020), not in PCCs/PGLs (P = .319). However, 25% of SDHx-HNPGLs lacked HIF-1α positive cells. CONCLUSION: As in PCCs/PGLs, SDHB immunohistochemistry in HNPGLs is a valuable method for identification of candidates for SDHx-genetic testing. On the contrary, although SDHx mutations may favor HIF-1α stabilization in HNPGLs, this is not a clinically useful biomarker.
BACKGROUND:Succinate dehydrogenase subunit B (SDHB) immunohistochemistry was considered a valuable tool to identify patients with inherited paraganglioma/pheochromocytoma (PGL/PCC). However, previous studies jointly analyzed 2 related but clinically distinct entities, parasympathetic head and neck paragangliomas (HNPGLs) and sympathetic PCCs/PGLs. Additionally, a role for hypoxia inducible factor-1α (HIF-1α) as a biomarker for succinate dehydrogenase (SDHx)-mutated tumors has not been studied. Here, we evaluated the utility of SDHB/HIF-1α proteins in HNPGLs and PCCs/PGLs as clinically useful biomarkers. METHODS: The SDHB/succinate dehydrogenase subunit A (SDHA)/HIF-1α immunohistochemistry analysis was performed in 158 genetically defined patients. RESULTS: Similarly to PCCs/PGLs, SDHB immune-negativity correlated with SDHx-mutations in HNPGLs (P < .0001). The HIF-1α stabilization was associated with SDHx-mutations in HNPGLs (P = .020), not in PCCs/PGLs (P = .319). However, 25% of SDHx-HNPGLs lacked HIF-1α positive cells. CONCLUSION: As in PCCs/PGLs, SDHB immunohistochemistry in HNPGLs is a valuable method for identification of candidates for SDHx-genetic testing. On the contrary, although SDHx mutations may favor HIF-1α stabilization in HNPGLs, this is not a clinically useful biomarker.
Authors: Neali Armstrong; Claire M Storey; Sarah E Noll; Katherine Margulis; Myat Han Soe; Haixia Xu; Benjamin Yeh; Lauren Fishbein; Electron Kebebew; Brooke E Howitt; Richard N Zare; Julien Sage; Justin P Annes Journal: Cell Rep Date: 2022-03-01 Impact factor: 9.995