Gene mutations and Hypoxia Inducible Factor (HIF-1) expression as prognostic-predictive factors in pheochromocytomas/paragangliomas (P/P) Abstract #99

Introduction: P/P are rare tumors sporadically associated with familial disorders. In advanced/unresectable disease, no standard treatment has so far been well established. Recently a mutation of some genes (SDHB, SDHC, SDHD) involved in the pathogenesis of familial P/P was discovered. These mutations are often associated with an over-expression of HIF-1, which plays a central role in angiogenesis and cell proliferation. This pathway is known to be inhibited by some targeted therapies, such as sunitinib or sorafenib.
Aim(s): To evaluate the expression of gene mutation and HIF-1 levels in P/P. In addition, these alterations as prognostic–predictive factors in P/P have been considered.
Materials and methods: A retrospective analysis of 30 P/P cases treated in our Istitute from 1999 to October 2009 was carried out. Nineteen patients had paragangliomas while the remaining 11 had pheochromocytomas. The main patient characteristics were: median age 49 yrs. (range 21-80); 16 males and 14 females; and the most common sites of disease were bone (36%), lymphnodes (30%), lung (16%), liver (16%). Twenty-six patients underwent resection of the primary tumor, while eight and 12 patients, respectively, were treated with chemotherapy and/or metabolic therapy. Additionally, in 12 patients the immunohistochemical evaluation of the SDHB mutation and the assessment of HIF-1 levels was carried out. The staining for SDHDB was optimized employing micro-slices of normal myocardial atrial muscle as positive control. To ensure antibody specificity, consecutive sections were incubated in absence of a primary antibody. The immunoreactivity was evaluated on a semiquantitative scale considering the extent (score 0-4) and the intensity (score 0-3) of staining. The product was used to obtain an immuno-staining score (total score 0-12).
Conference: 7th Annual ENETS Conference (2010)
Category: Basic
Presenting Author: Emilio Bajetta

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