Zinc alpha-2-glycoprotein is expressed by malignant prostatic epithelium and may serve as a potential serum marker for prostate cancer

Zinc alpha -2-glycoprotein (ZAG) is a M-r 41,000 glycoprotein secreted by a variety of normal epithelia, ZAG was recently shown to stimulate lipolysis in adipocytes, leading to the development of cachexia in animals with ZAG- producing tumors. To understand the possible contribution of ZAG to the dev elopment of cachexia in men with prostate cancer, ZAG production by normal and malignant prostate tissue was investigated using immunohistochemical as says. Anti-ZAG monoclonal antibodies reacted strongly with normal prostate epithelium but not with other components of prostate or seminal vesicles. T he majority of prostate cancers tested (35 of 48; 73%) also reacted with an ti-ZAG antibodies. High-grade tumors expressed significantly less ZAG than moderate-grade tumors (mean ZAG score 1.1 versus 1.9; P < 0.01). Men with Z AG-producing prostate carcinomas had elevated levels of serum ZAG relative to their normal age- and race-matched controls (P < 0.02). Furthermore, s.c . growth of human ZAG-producing murine tumors in syngeneic mice and orthoto pic growth of ZAG-producing human prostate carcinomas in nude rats resulted in readily detectable levels of human ZAG in the serum. Taken together, th ese studies show that ZAG production by prostate cancer can lead to systemi cally elevated serum ZAG levels that may be useful diagnostically. The effe cts of elevated systemic ZAG on cachexia-associated complications in patien ts with advanced prostate cancer deserves additional investigation.