IDENTIFICATION OF ONCOFETAL FIBRONECTIN IN PATIENTS WITH ADVANCED EPITHELIAL OVARIAN-CANCER - DETECTION IN ASCITIC FLUID AND LOCALIZATION TO PRIMARY SITES AND METASTATIC IMPLANTS

BACKGROUND. The mechanisms by which metastatic ovarian cancer adheres to peritoneal surfaces are not well understood. A role for tumor-deriv ed extracellular matrix adhesive molecules such as fibronectin (FN) ha s been proposed. Because oncofetal fibronectin (onfFN) isoforms functi on in the adhesion of trophoblasts and have been identified in associa tion with several malignancies, we sought to study onfFN in patients w ith advanced epithelial ovarian cancer. METHODS. Total FN was identifi ed with the nonspecific anti-FN monoclonal antibody CAF. OnfFN was ide ntified using the specific monoclonal antibodies FDC-6 and X18A4. Thes e antibodies were applied to: 1) ascitic fluid from advanced epithelia l ovarian cancer patients and peritoneal fluid from patients without p athologic conditions and 2) tissue sections of primary lesions and met astatic ovarian cancer implants. Comparative histologic specimens incl uded normal ovarian tissue and small bowel implants of endometriosis. RESULTS. When measured by sandwich enzyme-linked immunoadsorbent assay , all peritoneal fluids (32 malignant and 32 benign) contained marked quantities of total (CAF reactive) FN, although malignant ascites had higher concentrations than benign samples (173.2 +/- 36.8 mu g/mL vs. 76.4 +/- 31.8 mu g/mL; P = 0.001). Malignant ascites also had signific antly higher levels of onfFN than benign peritoneal fluid (FDC-6: 3.4 +/- 0.6 vs. 0.9 +/- 0.2 mu g/mL; and XI8A4: 5.1 +/- 1.3 vs. 1.1 +/- 0. 4 mu g/mL; P = 0.0001). Immunohistochemical staining of malignant lesi ons revealed prominent localization of both CAF reactive FN and onfFN to the stroma surrounding epithelial tumor nests. More delicate fibril lar staining within tumor nests also was evident. In contrast, implant s of endometriosis revealed strong stromal staining for CAF reactive F N but not for onfFN. CONCLUSIONS. These results demonstrate the presen ce of onfFN in advanced ovarian malignancies. We speculate that onfFN may participate in tumor-associated peritoneal adhesive interactions. (C) 1998 American Cancer Society.