Clear Cell Renal Cell Carcinoma (CCRC): Prognostic and Therapeutic Value of Angiogenesis
J Edeline, JJ Patard, C Vigneau, F Jouan, N Rioux-Leclercq. Facult de Mdecine, Universit de Rennes 1, Rennes, France; CHU Pontchaillou, Rennes, France
Background: Progress in the treatment of locally advanced or metastatic CCRC has been reported due to the emergence of anti-angiogenic therapies. Their efficacy raises a number of issues: better understanding of action mechanisms, identification of biological predictive factors for response/non response.
Design: Antiangiogenic drugs target CCRC angiogenesis via the VHL/VEGF/HIF pathway. The aim of the study is to analyze the prognostic value of angiogenesis in a prospective series of CCRC in correlation with clinicopathological factors and survival. 75 CCCR were included. Intratumoral vasculature was defined after histologic examination and CD31 immunostaining as type 1 mature and type 2 immature angiogenesis, in comparison with non tumoral kidney vascularization. Intratumoral microvascular density (MVD) was analyzed after immunostaining with CD31 as well as expression of VEGF-A, CAIX,and pVHL. VHL gene mutational analysis was performed using PCR/DNA sequencing and MLPA.
Results: Type 2 immature angiogenesis was significantly associated with high Fuhrman grade (p<0.0001), T stage (p<0.001), lymph node metastasis (p<0.03, M stage (p<0.002), low CAIX expression (p<0.002), high pVHL expression (p<0.001) and VEGF overexpression (p<0.0001). Type 2 vasculature was also associated with a low MVD (10+/-27.5) whereas type 1 angiogenesis was associated with high MVD (37.4 +/- 41.04) (p<0.0001). A significant association was found between VHL mutated CCRC, a less aggressive tumor profile and a type 1 angiogenesis (p<0.01). Moreover, patients with type 1 angiogenesis had improved survival, with a significant statistical difference compared with patients with type 2 angiogenesis (p<0.003).
Conclusions: CCRC seem to develop different pattern of angiogenesis: an immature vasculature associated with poor prognostic, and a mature angiogenesis associated with a favorable outcome. These types of blood vessels were also associated with different intratumoral expression of the VHL/HIF/VEGF pathway proteins. With the impact of antiangiogenic drugs, determination of the type of angiogenesis could define predicitve factors of response/non response, and patients who could benefit from these therapies. This work was supporting by grants of PNES REIN of Institut National du Cancer, France.
Category: Genitourinary (including renal tumors)
Wednesday, March 11, 2009 1:00 PM
Poster Session VI # 128, Wednesday Afternoon