The necessity for tumor markers which reflect tumor burden, patient response to therapy, and provide early indications of recurrent disease is an important and significant component for the present management of cancer patients. For gynecologic tumors no such markers existed. At this time, at least one promising tumor antigen CA125 has been documented and evaluated for use in serous ovarian cystadenocarcinomas. For ovarian cancer patients this finding has pertinence because of the latent nature of the disease in women in their post menopausal years. The proposal addresses the expression and characterization of CA125 in malignant ovarian carcinomas in benign disease and in normal tissues. Such information can impact a new understanding of continued or renewed expression of the gene in malignancy along with control of expression of the gene in normal tissue. It is proposed to study CA125 by utilizing a newly discovered source of the antigen in normal human tissues which previously was found only in trace amounts in mullerian duct derivatives. We have data which provides an insight into the subunit composition of the CA125 molecule and have developed polyclonal antibodies to the whole molecule. It is proposed to use this information and the polyclonal antibody reagent to evaluate the sub unit composition of the molecule from normal, benign and malignant tissues, to obtain sufficient amino acid sequence data for some of the subunits to be able to synthesize polynucleotide oligomers. These reagents will be used to probe a CDNA library made from chorion where a substantial concentration of CA125 antigen is located. The CDNA clones will be characterized for authenticity and used to screen and quantitate mRNA from normal and malignant tissues. In the future these probes will be further used to elucidate the structure and expression of the CA125 gene(s).
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