Urinary cancer-related protein EDC1 and serum inter-alpha trypsin inhibitor in breast cancer.

: In 1976 we isolated a novel glycoprotein labeled EDC1, Mr 27,500, which is immunologically related to the normal plasma protein inter-alpha trypsin inhibitor (IATI, Mr 160,000) and which is the major component of cancer-associated proteinuria. Urinary excretion of EDC1 (mg/g creatinine) may be classified in four ranges: i) low (less than 15); ii) light (15-30); iii) intermediate (31-45); and iv) heavy (greater than 45). Normal healthy women excrete 8.0 +/- 2.2 mg/g creatinine (average +/- SEM), whereas patients with metastatic breast cancer excrete 98.2 +/- 11.6 mg/g creatinine. Patients with a variety of non-malignant disorders excreted 14.6 +/- 4 mg EDC1/g creatinine, but patients with renal failure, rheumatoid arthritis, and infectious diseases averaged 130.3 +/- 60. Sixty-five to 95 percent of urinary immunoreactive EDC1 in the latter group was of higher molecular weight, perhaps reflecting increased renal clearance of plasma IATI. In patients undergoing excisional biopsy of breast lesions, preoperative EDC1 excretion was 21.5 +/- 3.4 in those whose lesions were benign and 43.1 +/- 7.6 in those whose lesions were malignant. Eight of these latter patients were heavy excretors; EDC1 excretion fell postoperatively in these patients. In normal serum the immunoreactive IATI (IR-IATI) exists in three molecular weight forms 160,000, 120,000 and 58,000. In patients who were heavy excretors of EDC1, the IR-IATI corresponding to Mr 58,000 was absent and total serum IR-IATI was about two-thirds of normal. There was also a negative correlation between serum levels of IATI and urinary EDC1 in these patients. These data suggest that urinary EDC1 may arise as a result of interaction between IATI and tumor-associated proteases.