DIAGNOSTIC IMPLICATIONS OF VIRAL PROTEINS IN CANCER

This project focuses on the development of the clinical consequences stemming from the discovery in human breast cancer of an antigen immunologically related to the 52,000 dalton glycoprotein (gp52) of the mouse mammary tumor virus. Interest in this crossreactive human antigen as a signal for breast malignancy was intensified by the finding that the plasma level of gp52 in the mouse proved to be an excellent diagnostic and prognostic indicator of disease status. Immunohistochemical examination of human breast cancer sections for the gp52-related protein revealed clinical correlates possessing some diagnostic usefulness. Thus, the level of the immunohistochemically detectable antigen is higher in the most aggressive breast cancers and appears to correlate with a poor prognosis. Further, women with a family history of breast cancer have a markedly higher probability of expressing this antigen in their malignant tissues. Finally, the immunohistochemical detection of the breast cancer antigen in lymph node and visceral metastases has correctly identified the presence of breast carcinoma in a number of patients who had no clinically detectable evidence of the primary lesion in the breast. The possibility that we will be able to use the human breast cancer antigen as a systemic signal of the disease has been greatly enhanced by the establishment ofa permanent human breast carcinoma cell line (47D). This line cnsistently secretes the breast cancer antigen encapsulated in virus-like particles in yields adequate for purification and for the generation of the requisite analytical immunological reagents. The investigations described in the body of this report detail the experiments required to convert the implied clinical potentials into usable reality. They include optimizing the production and the purification of the antigen of 47D and its clonal isolates and, most important, the production of hybridomas to gp52 and to particle proteins from the human breast cancer cell line (47D). These monoclonal antibodies should have the sensitivity and specificity needed to detect the antigen in the tissues and body fluids of breast cancer patients.