Vascular Expression of PDGFR- Isoform in Clear Cell Renal Cell Carcinoma: A Potential Therapeutic Marker?
A Petit, A Gaspa, X Garcia-Albeniz, A Nadal, B Mellado, C Mallofre. Hospital Clnic de Barcelona, Barcelona, Spain
Background: Growing understanding of the molecular biology of Clear Cell Renal Cell Carcinoma (CRCC) has established Vascular Endothelial Growth Factor (VEGF) and Platelet-Derived Growth Factor (PDGF) mediated tumor angiogenesis as relevant therapeutic targets in this tumor type. PDGF receptor (PDGFR) is a transmembrane tyrosine kinase with and isoforms. Recent works underline the important role of PDGFR in angiogenesis promotion by pericyte recruitment. Inhibitors targeting this tyrosine kinase have been proved effective controlling tumor growth in preclinical models and are undergoing clinical testing in metastatic CRCC patients. Despite its role in pathogenesis and as a therapeutic target in CRCC, little is known about the tissular expression of PDGFR in this tumor type. The aim of this study is to characterize the immunohistochemical expression of PDGFR in tissue samples of CRCC.
Design: Three TMA with representative areas from 97 CRCC formalin-fixed paraffin-embedded specimens were constructed. Immunohistochemical study was performed using polyclonal antibody against PDGFR (Santa Cruz, dilution 1:200). Expression of PDGFR on tumor cells and vessels was assessed independently and semiquantitatively. Regarding the expression on tumor cells both the extent and intensity of staining were taken into account in a three grade score: negative, low and high staining. Expression of PDGFR in tumor vessels was categorized as negative, focal (positivity in 25%of tumor vessels) and diffuse (positivity in >25% of tumor vessels).
Results: While 83,5% (81) CRCC showed no expression of PDGFR in tumor cells; low staining was seen in 12,4% (12) of cases and high in 4,1% (4) of them. In contrast, vascular expression of PDGFR was detected in 51,6% (50) cases, 29 of them exhibiting diffuse and 21 focal expression.
Conclusions: Our results highlight low expression of PDGFR in tumor cells and document for the first time, vascular expression of this receptor in CRCC tissue samples. This data supports the studies that propose PDGFR as an mediator of angiogenesis in this tumor. Differential PDGFR vascular expression seen among CRCC cases poses if tumors with diffuse vascular staining could be more sensible to target therapy against this receptor. The consideration of vascular expression of PDGFR as a therapeutic marker deserves further investigation and contrast with clinical trials testing PDGFR inhibitors.
Category: Genitourinary (including renal tumors)
Wednesday, March 11, 2009 1:00 PM
Poster Session VI # 108, Wednesday Afternoon