LOCAL CONCENTRATION OF FOLATE BINDING-PROTEIN GP38 IN SECTIONS OF HUMAN OVARIAN-CARCINOMA BY IN-VITRO QUANTITATIVE AUTORADIOGRAPHY

Folate binding protein (FBP) GP38 is a membrane-associated glycoprotei n that mediates the intracellular transport of folates. The enhanced e xpression of FBP in ovarian carcinomas provided a rational basis for c linical studies with specific monoclonal antibodies and some newly syn thesized antifolate drugs. Because the outcome of these clinical studi es ultimately depends on the degree of FBP expression, we measured the local concentration of FBP using I-125-MOv18 monoclonal antibody and quantitative autoradiography. Methods: Tissue sections from 37 specime ns of ovarian carcinoma and 13 nonmalignant ovaries were incubated wit h increasing concentrations of I-125-MOv18 with and without an excess of unlabeled antibody. Tissue-bound radioactivity was measured by quan titative autoradiography. Results: Folate binding protein was found to be overexpressed in 91% of nonmucinous ovarian carcinomas, with local concentrations ranging between 1.14 and 82.84 pmole/g, Adjacent tumor sections simultaneously studied with I-125-MOv18 and a I-125-labeled folio add derivative showed matching and superimposable regional distr ibutions of bound radioactivity of the two radioligands, indicating th at the antigen, specifically recognized by I-125-MOv18 in nonmucinous ovarian carcinomas, is capable of binding folates. Nonmalignant ovarie s did not contain measurable amounts of antigen when assayed with (125 )MOv18 but showed a limited and specific binding of the I-125-folic ac id derivative to tissue sections, The autoradiographic findings were c onfirmed by testing sections from mixtures of antigen-positive and ant igen-negative cells, by immunoperoxidase staining with MOv18 on tumor sections and by biochemical identification of FBP in membrane fraction s from tissue samples. Conclusion: Folate binding protein is overexpre ssed up to 80-90-fold in nonmucinous ovarian carcinomas compared with nonmalignant ovaries. Quantitation of FBP may provide a useful tool in the design of clinical studies with specific monoclonal antibodies an d certain antifolate drugs that enter the cell through FBP.