Introduction: Mutations in any of the subunits of the succinate dehydrogenase (SDH) complex predispose to PCC/PGL. Knowing the germline mutation is important for surveillance for recurrence, metastatic disease or more primary tumors and for screening affected family members. Expression of SDHB protein by immunohistochemistry (IHC) has been proposed as a surrogate marker for SDHx mutation status, with absent or decreased expression of SDHB suggesting the presence of a germline SDHB mutation or disruption of the SDH complex by mutation in another subunit.
Aim(s): To evaluate the effectiveness of SDHB IHC in predicting SDHx germline mutation status.
Materials and methods: We performed a retrospective review of the pathology reports between 2011-13 which included SDHB IHC on PCC/PGLs from patients with clinical genetic testing who either tested positive for SDHx germline mutation or had no identified mutation.
Conference: 11th Annual ENETS Conference (2014)
Category: Non digestive NETs (bronchial, MTC, pheochromocytoma)
Presenting Author: Lauren Fishbein
To read results and conclusion, please login ...
Further abstracts you may be interested in
Introduction: Paragangliomas (PGLs) are extra-adrenal, usually benign, highly vascularized tumors that originate from neural-crest-derived chromaffin cells. These tumors are subdivided as either sympathetic or parasympathetic, depending on their location and catecholamine production. Sympathetic PGLs are situated along the abdominal sympathetic trunk and usually produce catecholamines, whereas parasympathetic PGLs are located in the head and neck, and these usually do not produce catecholamines. PGLs may present as sporadic or inherited tumor syndrome, including MEN 2, with RET germline mutations, von Hippel-Lindau (VHL) disease due to germline mutations in VHL gene, and pheochromocytoma-PGL syndrome. The latter is frequently a hereditary condition and is caused by germline mutations in the SDHB, SDHC, or SDHC genes. Patients with familial PGLs may present at a younger age, often as multifocal tumors, with an increased risk of recurrence and a higher frequency of malignancy in those with SDHB mutations. SDH mutations induce angiogenesis and tumorogenesis through the inhibition of hypoxia-inducible factors (HIF)-propyl hyroxylase. A younger age at onset, malignancy, and a positive family history are clinical parameters of high specificity, but low sensitivity for diagnosis. Genetic analysis for mutations in SDH genes for the patient and family members, and surveillance for the affected patient and family members, are necessary where there are no clear clinical or family indicators for the syndrome. We present a case of a large abdominal malignant PGL in a 20-year-old pt. that went on without clinical detection for at least three years.
Conference: 7th Annual ENETS Conference (2010)
Presenting Author: Dr Mohammed Ahmed
Introduction: Gene mutations of the succinate dehydrogenase (SDH) complex are involved in the pathogenesis of cancer cells and play a pivotal role in angiogenesis and cell proliferation. The immunoistochemical (IHC) loss of SDHB is a marker of malignancy in pheocromocytomas and paragangliomas.
Conference: 10th Annual ENETS Conference (2013)
Category: Basic Science - mTOR and other pathways, signalling, receptors
Presenting Author: Md, PhD Massimo Milione
Introduction: Extra-adrenal paragangliomas (PGLs) occur as sporadic or familial entities, the latter mostly in association with germline mutations of the SDHB, SDHC or SDHD genes.
Conference: 8th Annual ENETS Conference (2011)
Presenting Author: Rita Domingues
Introduction: Absence of SDH subunit D (SDHD) mutations were reported by Perren et al (Oncogene 2002) but loss of heterozigosity (LOH) was described in 29% of the PETs. Since SDHD gene may depict a form of genomic imprinting in neuroendocrine (NE) tissue, the reported LOH may drive activation of the hypoxia pathway. Taking advantage from the immunohistochemical (IHC) method for genetic triage we may deduce the mutational status of SDH subunits (A, B, C and D) based on IHC SDHB expression. These subunits are striking candidates as they are mutated in other NE neoplasias.
Presenting Author: Mr João Vinagre
Introduction: The immunoistochemical (IHC) loss of SDHB expression was reported as a surrogate marker of malignancy in sporadic and familial pheocromocytomas/paragangliomas. SDHB loss is supposed to be tumorigenic (activation hypoxia signals).
Conference: 9th Annual ENETS Conference (2012)
Presenting Author: MD Sara Pusceddu