Increased Nicotinamide Phosphoribosyltransferase and Cystathionine-β-Synthase in Renal Oncocytomas, Renal Urothelial Carcinoma, and Renal Clear Cell Carcinoma

Abstract

Background: Renal oncocytomas (ROs), and clear cell (RCC) and urothelial carcinomas (UC), are common renal neoplasms. Nicotinamide phosphoribosyltransferase (Nampt) catalyzes the rate-limiting step of NAD⁺ synthesis and its expression is increased in several tumors. Nampt concomitantly regulates hydrogen sulfide (H₂S)-synthesizing enzyme levels, including cystathionine-β-synthase (CBS).

Materials and methods: We used tissue microarrays to examine Nampt and the H₂S-synthesizing enzyme CBS protein levels in benign kidney, RCC, UC and ROs.

Results: Compared to benign kidney, all three neoplasms showed increased Nampt and CBS protein levels, with the levels increasing in RCC at higher Fuhrman grades.

Conclusion: H₂S is known to ameliorate chronic renal failure but, as yet, no role for H₂S in renal neoplasia has been demonstrated. Here, we showed, for the first time, that Nampt, CBS and, likely, H₂S likely play a role in malignant and benign neoplastic renal disease.

Keywords: Fuhrman grade; Renal cancer; cystathionine-β-synthase; nicotinamide phosphoribosyltransferase.

Figure 1.

Representative high-power views of Nampt and CBS IHC. Benign renal cortex Nampt (A) and CBS (B). “*” denotes the proximal renal tubule, the arrow the distal renal tubule and “g” the glomerulus. RO Nampt (C) and CBS (D), renal UC Nampt (E) and CBS (F), Fuhrman grade I Nampt (G) and CBS (H), Fuhrman grade II Nampt (I) and CBS (J), Fuhrman grade III Nampt (K) and CBS (L), Fuhrman grade IV Nampt (M) and CBS (N). G through N are RCC. Nampt, Nicotinamide phosphoribosyltransferase; CBS, cystathionine-β-synthase; UC, urothelial carcinoma; RO, renal oncocytoma; IHC, immunohistochemistry.