Immunohistochemistry and Mutation Analysis of SDHx Genes in Carotid Paragangliomas

• Published in: International journal of molecular sciences Vol. 21; no. 18; p. 6950
• Main Authors: Snezhkina, Anastasiya V, Kalinin, Dmitry V, Pavlov, Vladislav S, Lukyanova, Elena N, Golovyuk, Alexander L, Fedorova, Maria S, Pudova, Elena A, Savvateeva, Maria V, Stepanov, Oleg A, Poloznikov, Andrey A, Demidova, Tatiana B, Melnikova, Nataliya V, Dmitriev, Alexey A, Krasnov, George S, Kudryavtseva, Anna V
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI 22.09.2020; MDPI AG
• Subjects: Adult; Carotid Body Tumor - enzymology; Carotid Body Tumor - genetics; Carotid Body Tumor - pathology; carotid paraganglioma; exome sequencing; Female; Humans; Immunohistochemistry; Male; Middle Aged; Mutation; mutations; Neoplasm Proteins - genetics; Neoplasm Proteins - metabolism; protein expression; SDHx genes; Succinate Dehydrogenase - genetics; Succinate Dehydrogenase - metabolism; exome sequencing; mutations; immunohistochemistry; SDHx genes; protein expression; carotid paraganglioma
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21186950

Carotid paragangliomas (CPGLs) are rare neuroendocrine tumors often associated with mutations in genes. The immunohistochemistry of succinate dehydrogenase (SDH) subunits has been considered a useful instrument for the prediction of mutations in paragangliomas/pheochromocytomas. We compared the mutation status of genes with the immunohistochemical (IHC) staining of SDH subunits in CPGLs. To identify pathogenic/likely pathogenic variants in genes, exome sequencing data analysis among 42 CPGL patients was performed. IHC staining of SDH subunits was carried out for all CPGLs studied. We encountered variants in 38% (16/42) of the cases in genes. IHC showed negative (5/15) or weak diffuse (10/15) SDHB staining in most tumors with variants in any of (94%, 15/16). In -mutated CPGL, SDHA expression was completely absent and weak diffuse SDHB staining was detected. Positive immunoreactivity for all SDH subunits was found in one case with a variant in . Notably, CPGL samples without variants in also demonstrated negative (2/11) or weak diffuse (9/11) SDHB staining (42%, 11/26). Obtained results indicate that SDH immunohistochemistry does not fully reflect the presence of mutations in the genes; diagnostic effectiveness of this method was 71%. However, given the high sensitivity of SDHB immunohistochemistry, it could be used for initial identifications of patients potentially carrying mutations for recommendation of genetic testing.