Cellular aspects of SDHD mutations in head and neck paragangliomas

Abstract

Introduction. Mutations in the SDHD gene, a nuclear gene encoding for a mitochondrial protein involved in oxidative phosphorylation, are responsible for the majority of hereditary head and neck paragangliomas. The aim was characterization of cellular manifestations of SDHD mutations in paragangliomas. Methods. Tumours of patients with and without inherited mutations were examined using electron microscopy, enzyme histochemistry and immunohistochemistry. Results. Ultrastructurally, large numbers of mitochondria with disturbed morphology were detected. In almost all cases, the SDH enzyme activity was virtually absent. The expression of two catalytic proteins in the SDH complex displayed two general patterns: the flavo protein was strongly upregulated, whereas the iron protein was reduced in the tumour cells. However, in some cases deviations from these patterns in enzyme activity and protein expression were observed. Conclusion. Cellular aspects of SDHD mutations are composed of increased numbers of mitochondria with disturbed morphology, reduced SDH enzyme activity and aberrant expression of catalytic components of the SDH complex. In some cases, deviations from these patterns are observed. Analysis of histopathological changes will lead to further understanding of the biology of paragangliomas and contribute to clinical treatment strategies in the future.