In order to determine whether succinate dehydrogenase (SDH) deficiency plays a role in spor-adic, non-familial pituitary adenomas, we analyzed 80 pituitary adenomas for SDH deficiency from patients without familial tumor syndromes or without known SDH deficiency-associated neoplasms. SDH deficiency was determined by immunohistochemical (IHC) stains for SDHB since the loss of any of the four SDH subunits results in the loss of SDHB expression. Three pituitary adenomas showed complete loss of SDHB staining, and of these two also showed loss of SDHA staining. We further characterized these adenomas by looking at Ki67, IGF1R, and 5-hmC levels via IHC. SDHx-deficient (non-SDHA deficient) tumors had a Ki67 proliferation index higher than non-SDH deficient pituitary tumors while SDHA-deficient tumors had Ki67 indices similar to non-SDH deficient tumors. IGF1R IHC staining was similar across all subsets. All SDH-deficient subtypes showed a loss of 5-hydroxymethylcytosine nuclear IHC staining. These findings suggest that SDH deficiency promotes tumorigenesis of pituitary adenomas through accumulation of succinate resulting in changes in the epigenome, specifically resulting in a hypermethylated state.
Recommended CitationAndrews, MD, Edward; Mardekian, MD, Stacey K.; Miettinen, Markku; and Curtis, MD, Mark T., "Succinate Dehydrogenase Deficiency in Sporadic Pituitary Adenomas: A Potential Mechanism for Tumorigenesis" (2014). Department of Pathology, Anatomy, and Cell Biology Resident's Posters. Paper 6.