Expression Patterns of Markers for Targeted Therapies in Renal Cell Carcinoma
SG Sharma, N Gokden. University of Arkansas for Medical Sciences, Little Rock, AR
Background: Renal cell carcinoma (RCC) is the classical example of the tumor with progress in the translational research and patient management. Many aspects of biology are focused for targeted therapy, such as anti-angiogenesis, anti-lymphangiogenesis, anti-COX-2, anti-EGFR and anti-protein kinase therapy. Anti-angiogenic therapy is the category 1 treatment now for relapse patients or stage IV patients with surgically unresectable tumors. The role of lymphangiogenesis and anti-EGFR and anti-cox-2 therapy is not clear in RCC. Anti protein-kinase therapy is still under clinical trials. The present study was designed to predict the possible targets for specific drug therapy.
Design: Retrospectively 33 cases were included in the study out of which 26 were clear cell RCC (cRCC) and 7 were papillary RCC (pRCC). To assess angiogenesis anti-VEGF A [VEGF-A] was used and the receptors assessed were Flt-1[for VEGF-1 using H-225], Flk-1[receptor for VEGF-2 using A-3]. The lymphangiogenesis was assessed using the antibody against VEGF-D [using H-144] and the receptor Flt-4 [antibody C-20]. The status of EGFR receptors was assessed using the Her-2, TYR-192H and TYR-1110. The involvement of protein kinase and Cox-2 was confirmed by P-TYR and Cox-2 staining. The staining was graded according to the number of positive cells and was reported as +, <10% of cells stained, ++, 10-50% positive and +++, >50% positive.
Results: VEGF D and Flt-4 are expressed 3+ in all grades of cRCC and in pRCC. VEGF A is 3+ expressed in higher grade cRCC while the receptor Flk1 is expressed in all grades of cRCC as well as pRCC. Flt-1 is not expressed widely in cRCC while it is 3+ expressed in pRCC. Anti-EGFR staining using antibody TYR-1092h showed a 3+ staining for all the grades of cRCC and the pRCC. Her-2 is not expressed in cRCC and pRCC. Cox-2 and P-TYR showed 1+ expression in cRCC and pRCC.
Conclusions: Lymphangiogenesis can be an important target for drug therapy using anti VEGF-D and anti-Flt-4. For targeting angiogenesis Flk1 is an important target for both cRCC and pRCC while VEGF-A can be targeted in higher grade cRCC. Flt 1 can be an important target in pRCC. EGFR receptor TYR (1092h) can be targeted in both cRCC and pRCC. Evaluation and further characterization of the expression patterns of these targets on tissue sections can have a potential impact on designing the specific targeted therapy.
Category: Genitourinary (including renal tumors)
Wednesday, March 24, 2010 9:30 AM
Poster Session V # 110, Wednesday Morning