Cyst fluid of ovarian cancer patients contains high concentrations of trypsinogen-2.
We have determined the concentrations of two tumor-associated trypsinogen (TAT) isoenzymes, called TAT-1 and TAT-2, in human ovarian tumor cyst fluid using monoclonal antibody-based immunofluorometric assays specific for each isoenzyme. TAT-1 and TAT-2 are immunologically indistinguishable from the two pancreatic trypsinogen isoenzymes, cationic trypsinogen (-1) and anionic trypsinogen (-2). Our results show that of the two isoenzymes TAT-2 is the predominant form in cyst fluid and its concentrations are significantly higher than the levels of the trypsinogen isoenzymes in serum and in preovulatory follicular fluid from hyperstimulated ovaries. The median concentration of TAT-2 was higher in mucinous than in serous cyst fluid as has been found previously for the specific trypsin inhibitor, tumor-associated trypsin inhibitor. Most notably, in mucinous cyst fluids the median level of TAT-2 was higher in borderline and malignant (2640 micrograms/liter) than in benign cases (84 micrograms/liter). Also in serous cyst fluids the TAT-2 level was higher in borderline and malignant (median 345 micrograms/liter) than in benign cases (median 18 micrograms/liter). In fluids from other types of malignant ovarian carcinomas slightly elevated levels of TAT-2 were also observed (median 62 micrograms/liter). The identity of the trypsinogens was verified by isolating them by immunoaffinity chromatography using monoclonal antibodies. The increased levels in association with malignancy suggest that TAT is involved in ovarian tumor dissemination and breakage of tissue barriers.
Koivunen
E
E
Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Finland.
Itkonen
O
O
Halila
H
H
Stenman
U H
UH
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor / Q000032:analysis*; D002850:Chromatography, Gel; D004591:Electrophoresis, Polyacrylamide Gel; D005122:Exudates and Transudates / Q000201:enzymology*; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D007527:Isoenzymes / Q000032:analysis* / Q000302:isolation & purification; D008875:Middle Aged; D008970:Molecular Weight; D010048:Ovarian Cysts / Q000201:enzymology*; D010051:Ovarian Neoplasms / Q000201:enzymology* / Q000601:surgery; D011863:Radioimmunoassay; D014362:Trypsinogen / Q000032:analysis* / Q000302:isolation & purification
D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; D007527:Isoenzymes; D014362:Trypsinogen