Immunohistochemistry Used to Investigate Genetic Link

By Robin Kunkel | December 19 2017

Figure 1. Paraganglioma (PGL) and pheochromocytoma (PCC) occurring in patients with germline succinate dehydrogenase (SDHx) subunit gene mutations. (A, D, G) Hematoxylin and eosin (H&E), (B, E, H) SDHB immunohistochemistry (IHC), and (C, F, I) fumarate hydratase (FH) IHC images from PGL/PCC from patients with known germline SDHx subunit mutations. The majority of tumors (86.4%) demonstrated loss of cytoplasmic SDHB IHC staining (B and E), although rare tumors showed either retained (H) or patchy (i.e., “indeterminate”) cytoplasmic SDHB IHC staining (data not shown). FH IHC staining was retained in all tumors (C, F, I). Magnification = 200X.

The work entitled The Utility of SDHB and FH Immunohistochemistry in Patients Evaluated for Hereditary Paraganglioma-Pheochromocytoma Syndromes by Aaron M. Udager, MD, PhD, and colleagues in the Department of Pathology was published in Human Pathology on October 24th, 2017. This work showed that, in the appropriate clinical settings, SDHB and FH immunohistochemistry (IHC) may be useful for identifying paraganglioma (PGL) and pheochromocytoma (PCC) patients for Medical Genetics evaluation.

Dr. Udager concludes that, “this study confirms the utility of SDHB IHC for identifying patients with germline mutations in succinate dehydrogenase (SDHx) subunit genes, although our results indicate that specific clinicopathologic parameters (i.e., PCC, head and neck PGL, etc.) may affect the positive predictive value of SDHB IHC in these specific contexts. In addition, awareness of potential false negative SDHB IHC results in PCC patients with germline von Hippel-Lindau (VHL) gene mutations may be helpful in the triage of molecular genetic testing when no germline mutations in SDHx subunit genes are identified. Finally, we describe the first reported assessment of fumarate hydratase (FH) IHC in PGL/PCC from patients evaluated for hereditary PGL/PCC syndromes and demonstrate that loss of cytoplasmic FH IHC may be associated with known germline FH mutations”.

The entire publication may be read here.

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