Measurement of a breast cancer associated antigen detected by monoclonal antibody SP-2 in sera of cancer patients

Abstract

An enzyme-linked immuno-absorbent assay has been developed for the detection of a circulating tumor-associated antigen, 90K, recognized by murine monoclonal antibody SP-2 (Iacobelli et al., Cancer Res 46: 3005-3010, 1986). This assay was found to be simple and reproducible. Using this method, 6% of 165 apparently healthy individuals and 15% of 91 patients with benign breast disease showed 90K levels above 1.7 units/ml. Approximately 50% of 129 patients with advanced breast cancer demonstrated serum antigen levels above 1.7 units/ml. All histological types of breast cancer were positive, and no association between the incidence of elevated 90K levels and other prognostic variables could be detected. The titers of 90K were significantly higher in sera from advanced-stage (3 and 4) patients than in those from patients with limited-stage (1 and 2) disease. Elevated 90K levels were also observed in patients with carcinomas of other sites, including gastrointestinal, gynecological, and lung tumors. By means of the immune blotting technique, the antigenic components carrying the determinants in serum and extracts of breast cancer cells have been identified. The levels of 90K did not correlate with those of CA 15-3 or CEA. The measurement of 90K in sera appears to be a useful adjunct to other available assays for the detection and monitoring of breast cancer and other malignant tumors.

Purification and characterization of a 90 kDa protein released from human tumors and tumor cell lines

“…This protein was found in more than 80% of breast cancers but not in non-cancerous normal mammary gland surrounding the cancer tissue [l]. Quantitation of 90K protein in the serum has been made possible by development of an ELISA assay with SP-2 mAbs [2]. Approximately 50% of patients with breast cancer, 40% of patients with gastrointestinal malignancies, and 30% of patients with gynecological malignancies, had elevated serum levels of the 90K protein [2].…”

“…Quantitation of 90K protein in the serum has been made possible by development of an ELISA assay with SP-2 mAbs [2]. Approximately 50% of patients with breast cancer, 40% of patients with gastrointestinal malignancies, and 30% of patients with gynecological malignancies, had elevated serum levels of the 90K protein [2]. More importantly, the assay has demonstrated that the fraction of patients showing elevated serum levels is greater for individuals with metastatic disease and that the level of 90K in serum correlates with cancer progression [2][3][4].…”

Expression of the 90K Immunostimulator Gene Is Controlled by a Promoter with Unique Features

“…90K is a secreted glycoprotein of 90 kDa, originally identified in the supernatant of human breast cancer cells (1,2). Purification and cloning revealed its identity to the binding protein of human Mac-2 (3), a soluble and membrane-associated lectin thought to play a role in cell adhesion and immune response, and high similarity to a mouse cyclophilin C-associated protein (4,5).…”

“…90K was detected in serum of healthy persons and, at elevated levels, in serum of patients suffering from various types of cancer (1,10), AIDS (7)(8)(9), or autoimmune diseases. 1 In many mammary carcinomas an inverse correlation was found between expression of 90K and mRNA levels of the HER2 receptor tyrosine kinase, a marker for poor prognosis for patients with breast cancer (2).…”

“…1 In many mammary carcinomas an inverse correlation was found between expression of 90K and mRNA levels of the HER2 receptor tyrosine kinase, a marker for poor prognosis for patients with breast cancer (2).…”