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Usefulness of Negative and Weak–Diffuse Pattern of SDHB Immunostaining in Assessment of SDH Mutations in Paragangliomas and Pheochromocytomas

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Abstract

This is a confirmatory study about usefulness of SDHB and SDHA immunostaining in assessment of SDH mutations in paragangliomas and pheochromocytomas. Paraganglioma/pheochromocytoma syndrome (PGL/PCC syndrome) consists of different entities, associated with germline mutations in five different genes: SDHD, SDHAF2, SDHC, SDHA and SDHB. It has been suggested that negative immunostaining of SDHB can be taken as an indicator of the presence of a mutation in one of the five SDH genes. We have performed SDHB and SDHA immunohistochemical staining in a series of paragangliomas and pheochromocytomas from 64 patients. The patients had been previously checked for mutations in SDHD, SDHC and SDHB, but also for mutation in RET and VHL. All 14 patients with SDH mutations (9 with SDHB and 5 with SDHD mutations) exhibited negative or weak–diffuse SDHB staining pattern in tumour tissue, whereas cells of the 23 RET mutated and 8 VHL mutated tumours showed a positive SDHB immunostaining. Sixteen of the patients that did not exhibit a mutation in any gene showed positive SDHB immunostaining in tumour tissue, while only three of the patients without mutation exhibited negative staining. All patients exhibited positive pattern of SDHA immunostaining. The results confirm the value of SDHB immunohistochemical status in assessment of germline mutations in PGL/PCC syndrome.

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Acknowledgments

This study was supported by grants, 2009SGR794, RD12/0036/0013, and Programa de Intensificación de la Investigación ISCIII. E.C. holds a predoctoral fellowship from AGAUR 2012FI-B2 00125. AdC is predoctoral fellows from La Caixa Fundation. Tumour samples were obtained with the support of Xarxa Catalana de Bancs de Tumours, the Tumour Banc Platform of RTICC and RD09/0076/00059, as well as the Spanish Tumour Bank Network coordinated by CNIO.

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Authors and Affiliations

  1. Department of Pathology and Molecular Genetics, and Research Laboratory, Arnau de Vilanova Universitary Hospital, University of Lleida IRBLLEIDA, Lleida, Spain

    Esmeralda Castelblanco, Maria Santacana, Joan Valls & Xavier Matias-Guiu

  2. National Cancer Research Centre (CNIO), Hereditary Endocrine Cancer Group, Madrid, Spain

    Aguirre de Cubas, Alberto Cascón & Mercedes Robledo

  3. Institute of Health Carlos III, Centre for Biomedical Research on Rare Diseases (CIBERER), Madrid, Spain

    Mercedes Robledo

  4. Department of Pathology and Molecular Genetics, Hospital Universitari Arnau de Vilanova, Av. Alcalde Rovira Roure 80, 25198, Lleida, Spain

    Xavier Matias-Guiu

Authors
  1. Esmeralda Castelblanco
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  2. Maria Santacana
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  7. Xavier Matias-Guiu
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Correspondence to Xavier Matias-Guiu.

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Castelblanco, E., Santacana, M., Valls, J. et al. Usefulness of Negative and Weak–Diffuse Pattern of SDHB Immunostaining in Assessment of SDH Mutations in Paragangliomas and Pheochromocytomas. Endocr Pathol 24, 199–205 (2013). https://doi.org/10.1007/s12022-013-9269-4

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  • DOI: https://doi.org/10.1007/s12022-013-9269-4

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