CA 125 in Ovarian Cancer: Advances and Controversy (Editorial‪)‬

Ovarian cancer continues to be a major health threat for women. The American Cancer Society estimates that in the United States in 1998, 25 400 new cases will be diagnosed and 14 500 women will die as a result of this disease (1). Most of these cancers are epithelial in origin, as germ cell tumors of the ovary represent only ~5% of the total. Approximately 70% of epithelial ovarian cancers will occur in women who are over the age of 50 years, and more than one-half of the women will be diagnosed with advanced disease. Thus, these women will have a 5-year survival rate of 30%. Certainly, there is great need for improved diagnostic methods to permit detection of this disease at an early stage, as well as more effective treatments for adenocarcinoma of the ovary. CA 125, the first serum tumor marker test for epithelial cancer of the ovary, was introduced by Bast et al. in 1983 (3). The murine monoclonal antibody (OC125) that is used to detect the CA 125 antigen was obtained after immunization with the OVCA 433 cell line (4). The original CA 125 test used the OC125 antibody as both the capture and indicator antibody in a radioimmunometric assay. More recently, the CA 125 II test has been developed, which uses the M 11 monoclonal antibody as the capture antibody for CA 125. A recent epitope-mapping workshop conducted by the International Society of Oncodevelopmental Biology and Medicine (ISOBM) has defined the binding characteristics of monoclonal antibodies reactive with CA 125 and has identified two major regions on the antigen, which are called OC125-like and M 11-like epitopes (5). The CA 125 antigen is actually a heterogeneous mixture of glycoproteins with a molecular weight range of 200-1000 kDa, but lower molecular weight species have also been reported (6). Much of the heterogeneity of the CA 125 antigen is most likely related to differences in glycosylation. The antigenic domains reactive with the monoclonal antibodies appear to be located on the protein part of the CA 125 molecule. CA 125 antigen is a cell membrane glycoprotein expressed by a variety of epithelial cells, and it is present in the circulation of patients with a variety of cancers, most notably ovarian cancer. Approximately one-half of the patients who have localized (Stage 1) ovarian cancer and 90% of patients with advanced disease (Stages 2-4) have increased serum concentrations of CA 125 (5). The CA 125 antigen is not specific for ovarian cancer, as serum increases are observed in some patients with cancers of the breast, endometrium, gastrointestinal tract, and lung. Benign diseases of the uterus, liver, and gastrointestinal tract and benign tumors of the ovary and uterus are also associated with increased concentrations of serum CA 125 (6).