Arginase-1 catalyzes the conversion of
arginine to
ornithine and
urea. Because of its predominant expression in hepatocytes, it serves as a marker for
hepatocellular carcinoma, although other
tumor entities can also express arginase-1. To comprehensively determine arginase-1 expression in normal and neoplastic tissues, tissue microarrays containing 14,912 samples from 117 different
tumor types and 608 samples of 76 different normal tissue types were analyzed by immunohistochemistry. In normal tissues, arginase-1 was expressed in the liver, the granular layer of the epidermis, and in granulocytes. Among
tumors, a nuclear and cytoplasmic arginase-1 immunostaining was predominantly observed in
hepatocellular carcinoma, where 96% of 49
cancers were at least moderately positive. Although 22 additional
tumor categories showed occasional
arginase immunostaining, strong staining was exceedingly rare in these entities. Staining of a few
tumor cells was observed in
squamous cell carcinomas of various sites. Staining typically involved maturing cells with the beginning of keratinization in these
tumors and was significantly associated with a low grade in 635
squamous cell carcinomas of various sites (p = 0.003).
Teratoma, urothelial
carcinoma and
pleomorphic adenomas sometimes also showed
arginase expression in areas with squamous differentiation. In summary, arginase-1 immunohistochemistry is highly sensitive and specific for
hepatocellular carcinoma if weak and focal staining is disregarded.