SDHB Mutation in High-Altitute Paraganglioma/Pheochromocytoma
Olga L Bohn, Sandra O Miranda-Symes, Silvia Montilla-Fonseca, Evelyn Cortez-Gutierrez, Sergio Sanchez-Sosa. Hospital Angeles, Puebla, Mexico; Hospital Juarez, Puebla, Mexico
Background: Pheochromocytomas/Paragangliomas (PPG) are components of several hereditary cancer syndromes, and up to 30% may be associated with germ line mutations of genes including VHL, RET and SDH. SDHB and SDHD encode proteins that regulate hypoxia-inducible factor 1 subunit alpha (HIF1α) that helps cells adapt to hypoxia. High levels of HIF1α can suppress SDHB, suggesting a hypoxic pattern in SDHB-mutant tumors. In this study we examine clinical and pathologic features of high-altitute PPG and determine SDHB mutation status.
Design: We reviewed twenty four PPG from Mexican patients living 2,000 m above sea level (Mexico City and Puebla) procured in our institution. Immunohistochemistry (IHC) was performed using antibodies for synaptophysin, chromogranin, S100 and SDHB. All cases were tested for genetic SDHB mutation. DNA extraction was carried out and SDHB gene was amplified by PCR.
Results: The mean age was 50 years (range 13-72) with a female predominance 7:1. The most common location was head and neck (19/24, 79.2%) followed by abdominal/pelvic region (3/24, 12.5%) and adrenal (2/24, 8.3%). PPG were positive for synaptophysin and chromogranin; S100 was positive in sustentacular cells. Patients with abdominal/pelvic PPG were members of the same family and had SDHB mutation in exon 6. In 3/3 abdominal/pelvic region and one adrenal PPG a loss of SDHB protein expression was observed. Eleven out of nineteen head and neck PPG had SDHB mutations involving exon 3, 4, 5 and 8; in three of these cases double mutation was found.
Conclusions: In Mexican patients, mutation in exon 5 of SDHB is present in high-altitute PPG of the head and neck. SDHB mutation in exon 6 is seen in familial PPG.
Wednesday, March 6, 2013 1:00 PM
Poster Session VI # 59, Wednesday Afternoon