Correlation of Immnunostains for Protein Expression with Genetic Abnormality of SDHB in Paraganglioma/Pheochromcytoma
Yu Liang, Shabirhusain S Abadin, Wei-Lian Wang, Nancy D Perrier, Alexander J Lazar. University of Texas MD Anderson Cancer Center, Houston, TX
Background: Pheochromocytomas (PCC) and paragangliomas (PGL) are rare tumors of chromaffin tissue in adrenal medulla and extraadrenal ganglia. Ten susceptibility genes are reported, accounting for ∼50% of the cases. The loss-of-function mutations of any of the 3 subunits of succinate dehydrogenase (SDHD, SDHC, and SDHB) have been recently associated with PCC/PGL by potentially activating the hypoxic gene response pathway. Immunostaining analysis may be able to identify tumors with mutations of SDH complex, triage patients for genetic testing, and potentially for treatment follow-up.
Design: We selected a group of PCC/PGL patients who underwent surgical resections and genetic testing at our institution from 1999 to 2012. Immunostains of SDHB were performed on paraffin-embedded tissue sections. The staining results were first evaluated blind to the genetic testing results, and the two sets of results were compared. The patient group (n=27; 10 females and 17 males) had a wide age range (22 y/o to 77 y/o) at the first diagnosis.
Results: Among the 20 patients with no abnormality of the SDHB gene (neither mutation nor deletion of SDHB gene, and documented alternative gene abnormality, e.g. VHL gene), 9 were stained positive for SDHB. All 7 patients with documented SDHB gene abnormality stained negative for SDHB for a specificity of 100%. Thus the positive predictive value of positive SDHB immunostain for no genetic abnormality is also 100%.
Conclusions: Our data suggests that intact staining for SDHB indicates a lack of mutation in the SDH family. Loss of SDH in the absence of documented SDHB mutation may suggest that another member of the SDH family is mutated or lost.
Wednesday, March 6, 2013 1:00 PM
Poster Session VI # 60, Wednesday Afternoon