Clinical significance and peculiarities of succinate dehydrogenase B and hypoxia inducible factor 1 alpha expression in parasympathetic versus sympathetic paragangliomas
Por:
Bernardo-Castineira C, Saenz-de-Santa-Maria I, Valdes N, Astudillo A, Balbin M, Pitiot A, Jimenez-Fonseca P, Scola B, Tena I, Molina-Garrido M, Sevilla M, Beristein E, Forga L, Villabona C, Oriola J, Halperin I, Suarez C, Chiara M
Publicada:
1 ene 2019
Resumen:
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-1 alpha (HIF-1 alpha) as a biomarker for succinate dehydrogenase (SDHx)-mutated tumors has not been studied. Here, we evaluated the utility of SDHB/HIF-1 alpha proteins in HNPGLs and PCCs/PGLs as clinically useful biomarkers. Methods The SDHB/succinate dehydrogenase subunit A (SDHA)/HIF-1 alpha 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-1 alpha stabilization was associated with SDHx-mutations in HNPGLs (P = .020), not in PCCs/PGLs (P = .319). However, 25% of SDHx-HNPGLs lacked HIF-1 alpha 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-1 alpha stabilization in HNPGLs, this is not a clinically useful biomarker.
Filiaciones:
Bernardo-Castineira C:
Univ Oviedo, Hosp Cent Asturias, Inst Sanitary Res Asturias, Inst Oncol Asturias IUOPA,CIBERONC, Oviedo, Spain
Saenz-de-Santa-Maria I:
Univ Oviedo, Hosp Cent Asturias, Inst Sanitary Res Asturias, Inst Oncol Asturias IUOPA,CIBERONC, Oviedo, Spain
Valdes N:
Hosp Cent Asturias, Serv Endocrinol & Nutr, Oviedo, Spain
Astudillo A:
Hosp Cent Asturias, Serv Pathol, Oviedo, Spain
Balbin M:
Hosp Cent Asturias, Serv Mol Oncol, Oviedo, Spain
Pitiot A:
Hosp Cent Asturias, Serv Mol Oncol, Oviedo, Spain
Jimenez-Fonseca P:
Hosp Cent Asturias, Serv Med Oncol, Oviedo, Spain
Scola B:
Hosp Gregorio Maranon, Serv Otorhinolaryngol, Madrid, Spain
Tena I:
Hosp Prov Castellon, Serv Med Oncol, Castellon de La Plana, Spain
Molina-Garrido M:
Hosp Gen Virgen Luz, Serv Med Oncol, Cuenca, Spain
Sevilla M:
Hosp Virgen Rocio, Serv Otorhinolaryngol, Seville, Spain
Beristein E:
Hosp Univ Araba Txagorritxu, Lab Mol Genet, Vitoria, Spain
Forga L:
Complejo Hosp Navarra, Serv Endocrinol & Nutr, Pamplona, Spain
Villabona C:
Hosp Univ Bellvitge, Serv Endocrinol & Nutr, Barcelona, Spain
Oriola J:
Hosp Clin Barcelona, Lab Biochem & Mol Genet & Endocrinol & Nutr Sci, Barcelona, Spain
Halperin I:
Hosp Clin Barcelona, Lab Biochem & Mol Genet & Endocrinol & Nutr Sci, Barcelona, Spain
Suarez C:
Hosp Cent Asturias, Serv Otorhinolaryngol, Oviedo, Spain
Chiara M:
Univ Oviedo, Hosp Cent Asturias, Inst Sanitary Res Asturias, Inst Oncol Asturias IUOPA,CIBERONC, Oviedo, Spain
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