Increased Nicotinamide Phosphoribosyltransferase in Rhabdomyosarcomas and Leiomyosarcomas Compared to Skeletal and Smooth Muscle Tissue

Abstract

Nicotinamide phosphoribosyltransferase (NAMPT) catalyzes the rate-limiting step in NAD synthesis and is up-regulated in several human malignancies, including breast, colon, prostate, thyroid, gastric, and several hematopoietic malignancies. In some malignancies, such as gastric, thyroid, and prostate carcinomas, higher NAMPT expression correlates with deeper tumor invasion, increased metastatic potential and chemotherapy resistance. We employed tissue microarray immunohistochemistry to examine NAMPT expression in benign skeletal and smooth muscle, leiomyomas, leiomyosarcomas (graded low-, intermediate-, and high-grade), and spindle, embryonal, pleomorphic, and alveolar rhabdomyosarcomas. We found low to intermediate NAMPT expression in benign tissue, leiomyomas, leiomyosarcomas (low- and intermediate-grades), and spindle cell rhabdomyosarcomas. In contrast, high-grade leiomyosarcomas and embryonal, alveolar, and pleomorphic rhabdomyosarcomas showed high NAMPT expression. Herein we show for the first time that NAMPT is overexpressed in certain sarcoma types and the level of NAMPT expression correlates with tumor behavior.

Keywords: NAMPT; leiomyoma; leiomyosarcoma; rhabdomyosarcoma; skeletal muscle; smooth muscle.