A system of cancer-related urinary glycoproteins: biochemical properties and clinical applications

Abstract

Gel-filtration and immunodiffusion reveal most patients with disseminated cancer excrete 100 to 1000 mg/day of urine proteins, mol wt 10,000-60,000, which are distinct from known plasma proteins and cancer-related antigens. By gel-filtration and ion-exchange chromatography, 5 novel urinary glycoproteins have been isolated which are responsible for about 1/2 the mass of the "low molecular weight proteinuria" of patients with advanced cancer: BJC1 and BJC2 (patient B.J., chronic myelocytic leukemia); JBB5 (J.B., metastatic pancreatic carcinoma); EDC1 (E.D., acute myelocytic leukemia); HNC1beta (H.N., acute monocytic leukemia). Mol wts respectively are 29,000, 22,000, 55,000, 27,000 and 33,000, and carbohydrate contents respectively 61%, 23%, 23%, 27% and 40%. Attention to date has focussed on EDC1 and HNC1beta, because their urinary excretion directly reflects the course of the neoplastic disease. EDC1 and HNC1beta possess the same protein but different carbohydrate moieties. They are antigenically related to inter-alpha trypsin inhibitor, mol wt 160,000, which is one of the 6 antiproteolytic proteins in normal human plasma. EDC1 and HNC1beta both possess antitryptic activity. Specific radioimmunoassays (RIA) to these 2 glycoproteins were developed. Normal individuals (n = 210) excreted 0.3 +/- .02 (ave. +/- SE) mg EDC1 per g creatinine. In 18 non-neoplastic diseases (n = 75), urinary EDC1 was .5 +/- .06 mg/g creatinine. In disseminated cancer of 7 types (n = 81) (breast, ovary, colon, squamous of head-neck and lung; melanoma; acute myelocytic leukemia), ave. EDC1 excretion ranged from 10 to 190 mg/g creatinine. A significant increase (P less than .05) was found in the localized stage of squamous cancer of head-neck-lung, but only after regional or distant spread in the other types. Similar results were found with HNC1beta, urinary excretion of which averaged 1/10 that of EDC1. Effective chemotherapy in 5 patients with leukemia or solid tumors caused prompt disappearance of urinary EDC1; the glyco-protein reappeared in the urine several weeks before clinical relapse.

Conclusions: (i) EDC1- and HNC1beta-proteinuria is a useful indicator of some types of localized and most types of disseminated cancer; (ii) the degree of this proteinuria reflects the effectiveness of chemotherapy; (iii) the antiproteolytic property of EDC1 and HNC1beta suggests a relation between proteolysis and tumorigenesis.