Genetic testing and immunohistochemistry for SDHB in phaeochromocytoma-paraganglioma syndromes: the South Australian experience

Poplawski, NK; Rawlings, Lesley; Seymour, John F.; Vakulin, Cassandra; Tirimacco, Amanda; Benn, DE; Gill, Anthony J.

doi:10.1186/1897-4287-10-s2-a60

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“…Hereditary PC/PGL syndrome can be caused by germline mutations in any of the SDH subunits as well as in SDHAF2, a mitochondrial protein that flavinates SDHA and promotes maturation of SDHB. 16,[21][22][23][24] The reported rate of SDH mutations in PGLs varies significantly between series, ranging from 15% to 54%. 15,25 Mutations in SDHB and SDHD are the most common of the four subunits and correspond to syndromes PGL4 and PGL1 respectively.…”

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confidence: 99%

Prevalence of succinate dehydrogenase deficiency in paragangliomas and phaeochromocytomas at a tertiary hospital in Cape Town: a retrospective review

Bruce-Brand

Wyk

2020

Journal of Endocrinology, Metabolism and Diabetes of South Afri

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Introduction: A substantial proportion of phaeochromocytomas and paragangliomas are associated with underlying germline mutations, of which the majority are due to mutations in one of the genes in the succinate dehydrogenase (SDH) complex. A commercially available immunohistochemical stain for SDHB has excellent correlation with SDH gene mutation status when staining is lost. This abnormal loss of staining can identify potential familial tumours and tumours with a higher risk of malignant behaviour. The prevalence of SDH deficiency in the South African setting has not been published previously. Methods: A retrospective laboratory-based study at Tygerberg Hospital in Cape Town used immunohistochemistry on archived tumour tissue to assess loss of SDHB staining in phaeochromocytomas and paragangliomas submitted to the histopathology laboratory (National Health Laboratory Service) between 2005 and 2015. Results: Tumour tissue from 52 patients was tested. In total, 36% showed loss of staining. Loss of staining was significantly correlated with a younger age at presentation (z = −3.59, p < 0.001). The median age of those who showed loss of staining was 26 years (IQR 21-41), compared with 50.5 years (IQR 36-61) for those who showed retained staining. The interobserver agreement in the interpretation of the immunohistochemical stain was excellent (Cohen's kappa = 0.917; 95% confidence interval, 0.81-1, p < 0.001). Conclusion: Approximately one-third of phaeochromocytomas and paragangliomas in our setting are likely to be associated with germline mutations in one of the SDH genes. Immunohistochemical testing of tumour tissue can identify this group to allow better prognostication and appropriate genetic testing and counselling.

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