SDHB Negative Staining as an Indicator of Presence of SDHB, SDHC and SDHD Germ Line Mutations in Pheocromocytomas and Paragangliomas
Esmeralda Castelblanco, Sonia Gatius, Judith Pallares, Maria Santacana, Aguirre de Cubas, Alberto Cascon, Mercedes Robledo, Xavier Matias-Guiu. Hospital Universitari Arnau de Vilanova, University of Lleida, IRB Lleida, Lleida, Catalunya, Spain; Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Spain
Background: Pheocromocytoma (PCC) and paragangliomas (PGL) can occur sporadically or as a part of several different hereditary tumor syndromes. The PGL/PCC syndrome is associated with different germline mutations in SDHD, SDHAF2, SDHC and SDHB. Negative staining of SDHB has been proposed as an indicator of the presence of SDHB, SDHC and SDHD germline mutations. Our aim was to confirm the usefulness of SDHB negative staining as a predictor of the presence of SDHB, SDHC and SDHD germline mutations in a series of PCC and PGL.
Design: Sixty-four tumors (36 adrenal PCC, 11 thoracic-abdominal PGL and 17 head and neck PGL) were assessed for SDHB immunostaining. Mutational status of SDHD, SDHAF2, SHDC, SDHB, RET, VHL, was assessed in normal and tumor tissue.
Results: SDHB staining was negative or granular-like in 17 cases (27%) and positive in 47 (73%). A germ line SDHB mutation was detected in 9 patients (7 with negative and 2 with granular-like staining). SDHD germline mutation was detected in 5 patients (all 5 with granular like staining). Germline mutations in RET (23 patients) and VHL (8 patients) were always associated with positive SDHB immunostaining. Nineteen patients showed absence of any germline mutation; SDHB positive stain was seen in 16 cases, while 3 of them had negative staining.
Conclusions: SDHB negative staining is a sensitive and cost effective screening tool for patients with PCC and PGL, since the vast majority of tumors with negative SDHB immunostaing were associated with germline mutations in SDH genes.
Wednesday, March 6, 2013 1:00 PM
Poster Session VI # 61, Wednesday Afternoon