Arginine metabolism in soft tissue sarcoma

Background: l-Arginine (l-Arg) is a conditionally essential amino acid for humans, which is the substrate for both arginase (ARG) and the inducible form of nitric oxide synthase (iNOS) enzymes. Whether l-Arg metabolism has detrimental or beneficial influence on the tumor growth depends on local up regulation of the NOS or ARG pathways at the tumor site. Objective: To evaluate the expression profile of ARG and iNOS in various histological subtypes of soft tissue sarcomas (STSs). Methods: A series of 81 adult STSs were tested for ARG1, ARG2 and iNOS expression by immunohistochemical analysis. Results: ARG1, ARG2 and iNOS expression was found in tumor cells of all cases of STSs except dermatofibrosarcoma protuberans (DFSP) in a cytoplasmic pattern. However, there was no significant correlation found between ARG, iNOS expression and histopathological parameters. Conversely, the majority of DFSP were devoid of ARG and iNOS expression, while only two cases showed focal and weak expression. Conclusions: Overexpression of l-Arg-metabolizing enzymes ARG and iNOS in tumor cells of all of the STS cases except DFSP may have a role in mediating the biological processes which characterize STSs. New knowledge of the regulation of arginine metabolism in tumor tissues is key to designing sound therapeutic means to effectively prevent tumorigenesis. Further studies are needed to clarify the absence of ARG and iNOS staining in DFSP.