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Clinical Trial
. 2020 Sep 22;21(18):6950.
doi: 10.3390/ijms21186950.

Immunohistochemistry and Mutation Analysis of SDHx Genes in Carotid Paragangliomas

Anastasiya V Snezhkina  1 , Dmitry V Kalinin  2 , Vladislav S Pavlov  1 , Elena N Lukyanova  1 , Alexander L Golovyuk  2 , Maria S Fedorova  1 , Elena A Pudova  1 , Maria V Savvateeva  1 , Oleg A Stepanov  1 , Andrey A Poloznikov  3 , Tatiana B Demidova  4 , Nataliya V Melnikova  1 , Alexey A Dmitriev  1 , George S Krasnov  1 , Anna V Kudryavtseva  1
Affiliations
Clinical Trial

Immunohistochemistry and Mutation Analysis of SDHx Genes in Carotid Paragangliomas

Anastasiya V Snezhkina et al. Int J Mol Sci. .

Abstract

Carotid paragangliomas (CPGLs) are rare neuroendocrine tumors often associated with mutations in SDHx genes. The immunohistochemistry of succinate dehydrogenase (SDH) subunits has been considered a useful instrument for the prediction of SDHx mutations in paragangliomas/pheochromocytomas. We compared the mutation status of SDHx genes with the immunohistochemical (IHC) staining of SDH subunits in CPGLs. To identify pathogenic/likely pathogenic variants in SDHx 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 SDHx variants in 38% (16/42) of the cases in SDHx genes. IHC showed negative (5/15) or weak diffuse (10/15) SDHB staining in most tumors with variants in any of SDHx (94%, 15/16). In SDHA-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 SDHD. Notably, CPGL samples without variants in SDHx 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 SDHx mutations for recommendation of genetic testing.

Keywords: SDHx genes; carotid paraganglioma; exome sequencing; immunohistochemistry; mutations; protein expression.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Distribution of SDHx variants in patients with CPGLs. Yellow dots—patients with SDHD variants, green dots—patients with SDHC variants, red dots—patients with SDHB variants, blue dot—patient with SDHA variant, grey dots—patients with no mutations in SDHx.
Figure 2
Figure 2
Representative images of SDHB immunostaining in CPGLs. (+) positive, (*) weak diffuse, (-) negative. Magnification x400.
See this image and copyright information in PMC

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