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Department of Genetics and Microbial Biology, University of Milan [J. B., N. P.], and Department of Biology and Biotechnology, San Raffaele Scientific Institute, 20132 Milan, Italy [C. F. M. S., F. B.]; Finsen Laboratory, Rigshospitalet, 2100 Copenhagen Ø, Denmark [R. S., K. D., N. B.]; and Department of Gynecology and Obstetrics, San Raffaele Hospital, 20132 Milan, Italy [A. M., M. B., L. F., A. F.]
Ascites and serum of patients with ovarian carcinoma contain a soluble form of urokinase-type plasminogen activator receptor (uPAR). We now report that pro-uPA-Sepharose-purified uPAR from ascites of patients with ovarian carcinoma is the full-length molecule missing the glycosylphosphatidylinositol anchor, as determined by its amino acid composition.
We next examined the significance of determining serum soluble uPAR (suPAR) levels in ovarian cancer patients using a specific ELISA and compared the results with serum concentrations of CA-125, an established diagnostic marker. Serum from pre- and postoperative ovarian cancer patients was assayed for suPAR and CA-125. The majority of the patients with ovarian cancer had enhanced preoperative serum levels of suPAR compared with healthy controls, but suPAR concentrations decreased after operation. Although uPAR was associated with most ovarian carcinomas, it appeared to be a less specific indicator for ovarian cancer than CA-125. On the other hand, suPAR was more specific for other types of solid tumors. Moreover, we have observed some cases of ovarian cancer that showed increase of suPAR but not of CA-125.
The prognostic significance of serum suPAR assay for survival of ovarian carcinoma patients was evaluated using Cox's proportional hazards analysis. Our preliminary data show that high preoperative levels of suPAR were associated with worse survival of the patients, whereas CA-125 had no prognostic implications.
This is the first report evaluating the assay of serum suPAR levels in ovarian cancer and analyzing its value as a tumor or prognostic marker.
1 This work was supported by grants from the Italian Association for Cancer Research, the Biomed-2 Program of the European Union, and the Danish Cancer Society. C. F. M. S. and J. B. were fellows of the European Association for Cancer Research.
2 Present address: Cancer Research Institute, Spitalska 21, Bratislava, Slovakia.
3 Present address: The Protein Laboratory, Panum Institute, Blegdamsvej 3, Copenhagen, Denmark.
4 To whom requests for reprints should be addressed, at Dipartimento di Ricerca Biologica e Tecnologica, H. S. Raffaele, via Olgettina 58, 20132 Milan, Italy. Phone: 39-2-2643 4832; Fax: 39-2-2643 4844; E-mail: Blasif@dibit.hsr.it.
Received 11/ 3/97. Accepted 3/ 4/98.
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