Paradoxal Loss of PDGF-CC Expression in Pheochromocytomas and Paragangliomas.
Andre Pinto, Victoria Sujoy, Ulf Eriksson, Munro Neville, Vania Nose. Jackson Memorial Hospial/University of Miami, Miami, FL; Ludwig Institute for Cancer Research, Karolinska Institute, Stockholm, Sweden
Background: Physiologically, platelet-derived growth factors (PDGFs) have been demonstrated to play a role in the angiogenesis and embryonic development of kidney, brain, cardiovascular and respiratory systems. Pathologically, these factors have been implicated in the genesis of a number of tumor types. They belong to a growth factor family that exert their cellular effects through PDGF-α and PDGF-β protein tyrosine kinase receptors. More recently, a new member of the family of PDGFs (CC) has been reported to have similar effects as PDGF AA and BB.
It was previously shown that PDGFR is overly expressed in the normal adrenal gland cells. However, its role in this organ environment and if it plays a role on adrenal tumorigenesis is not yet well known. Initial studies are showing that drugs that inhibit PDGFs may be therapeutically effective for treatment of paragangliomas and pheochromocytomas. Our objective was to define the relationship between a specific subtype of PDGF (CC) and distinct types of adrenal lesions, to investigate if there is an overexpression or loss in any hyperplasia or neoplasia.
Design: We studied the reactivity to PDGF-CC by immunohistochemistry in normal adrenal glands and in forty cases of adrenal cortical hyperplasia and neoplasia, pheochromocytomas (including sporadic and familial syndromes- MEN, VHL, SDHB),
paragangliomas, neuromas, ganglioneuromas and ganglioneuroblastomas.
Results: We found that normal adrenals expressed PDGF-CC reactivity in both cortex (ranging from 1+ to 2+) and medulla (3+). Sustentacular and endothelial cells also showed intense positivity to the antibody. However, 100% of the pheochromocytomas and paragangliomas completely lost their expression of PDGF-CC. Other medullary tumors and cortical lesions had a variable expression profile (ranging from 1+ to 2+).
Conclusions: Although some initial clinical trials are showing effectiveness of PDGFRs inhibitors in the treatment of pheochromocytomas and paragangliomas, the analysis of PDGFR-CC expression on adrenal cells showed a paradoxically loss of this marker and tumor progression. Additional studies are necessary to demonstrate if this phenomenon has any relation with tumorigenesis, and also to reveal if this receptor selectiveness would play any role in future therapeutic interventions.
Tuesday, March 1, 2011 1:00 PM
Poster Session IV # 48, Tuesday Afternoon