336 Increased Nicotinamide Phosphoribosyltransferase and Cystathionine B-Synthase in Renal Oncocytomas, Renal Transitional Cell Carcinoma, and Renal Cell Carcinoma

Abstract

Renal cell carcinoma (RCC) and transitional cell carcinoma (TCC) are the two most common renal malignancies, while renal oncocytomas are common benign renal neoplasms. Nicotinamide phosphoribosyltransferase (Nampt) catalyzes the rate-limiting step in nicotinamide adenine dinucleotide synthesis, while cystathionine B-synthase (CBS) catalyzes H2S synthesis. Both Nampt and CBS show concomitant increased expression in some tumors, with their expression positively correlating with higher tumor grade. We employed tissue microarray studies to analyze Nampt and CBS protein levels in benign renal cortex, RCC, TCC, and renal oncocytoma tissue samples. For Nampt, 29 benign, 49 TCCs, 94 RCCs, and six oncocytomas were examined. For CBS, 11 benign, 53 TCCs, 101 RCCs, and six oncocytomas were examined. The expression of both proteins was increased in TCC, RCC, and oncocytomas, compared to benign renal tissue. In RCC, the expression of both enzymes increased with increasing Fuhrman grade. To our knowledge, this is the first demonstration that Nampt and CBS are increased in renal RCC, TCC, and oncocytomas, and also increased with increasing RCC grade. Both enzymes promote tumor growth, survival, and angiogenesis in several malignancies. Increased expression of either enzyme in any oncocytoma type has not been previously reported. While preliminary, our data indicate that increased in Nampt and CBS protein expression, and possibly changes in H2S metabolism may have a role in benign and malignant renal neoplasia.