The loss of succinate dehydrogenase B expression is frequently identified in hemangioblastoma of the central nervous system

Tae Hoon Roh,Jin Roh,Se-Hyuk Kim,Hyunee Yim,Jang-Hee Kim,So Hyun Park,Kyi Beom Lee,Seon-Yong Jeong

doi:10.1038/s41598-019-42338-z

Tae Hoon Roh, Jin Roh + Show 6 more

Open Access

https://doi.org/10.1038/s41598-019-42338-z

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Journal: Scientific Reports	Publication Date: Apr 10, 2019
Citations: 9	License type: open-access

Affiliation: Ajou University

Abstract

Succinate dehydrogenase (SDH) is a mitochondrial enzyme that plays an important role in both the Krebs cycle and the electron transport chain. SDH inactivation is associated with tumorigenesis in certain types of tumor. SDH consists of subunits A, B, C and D (SDHA, SDHB, SDHC, and SDHD, respectively). Immunohistochemistry for SDHB is a reliable method for detecting the inactivation of SDH by mutations in SDHA, SDHB, SDHC, SDHD and SDH complex assembly factor 2 (SDHAF2) genes with high sensitivity and specificity. SDHB immunohistochemistry has been used to examine the inactivation of SDH in various types of tumors. However, data on central nervous system (CNS) tumors are very limited. In the present study, we investigated the loss of SDHB immunoexpression in 90 cases of CNS tumors. Among the 90 cases of CNS tumors, only three cases of hemangioblastoma showed loss of SDHB immunoexpression. We further investigated SDHB immunoexpression in 35 cases of hemangioblastoma and found that 28 (80%) showed either negative or weak-diffuse pattern of SDHB immunoexpression, which suggests the inactivation of SDH. Our results suggest that SDH inactivation may represent an alternative pathway in the tumorigenesis of hemangioblastoma.

Highlights

Succinate dehydrogenase (SDH) is an important mitochondrial enzyme that participates in the Krebs cycle and the electron transport chain[1,2]
SDHB immunonegativity has been reported in pheochromocytoma/paraganglioma, gastrointestinal stromal tumors (GISTs), renal cell carcinomas (RCCs), pituitary adenomas (PAs), pancreatic neuroendocrine tumors (NETs), prostate cancer, stomach cancer, and testicular seminoma[15,20,22,23,24,27,31]
80% of hemangioblastomas showed either negative or weak-diffuse pattern of SDHB immunoexpression, which suggests the inactivation of SDH

Summary

Introduction

Succinate dehydrogenase (SDH) is an important mitochondrial enzyme that participates in the Krebs cycle and the electron transport chain[1,2]. It consists of four subunits: SDHA, SDHB, SDHC, and SDHD. SDH inactivation results in the accumulation of succinate and induces the stabilization of hypoxia-inducible factor (HIF) via competitive inhibition of HIF prolyl-hydroxylases. To the best of our knowledge, the loss of SDHB immunoexpression has not been explored in various types of CNS tumors. We performed SDHB immunohistochemistry in various types of CNS tumors and found a significant proportion of hemangioblastomas with loss of SDHB immunoexpression

Methods

Results

Conclusion