Tumorassoziierte Antigene und Fibrinderivate als Reaktionsprodukte des Ovarialkarzinoms

Abstract
The detection of tumour-associated antigens in blood, ascites fluid, and tissue by the use of monoclonal antibodies establishes new aspects for the course control of ovarian cancer therapy and the evaluation of tumour-associated fibrinolysis. Monoclonal antibodies to the cross-linking site of fibrin derivatives in an enzyme immunoassay (D-dimer-ELISA) allow to compare quantitative results of fibrinolysis products with different tumour markers and the clinical tumour situation. In a prospective follow-up-study in 102 patients with epithelial ovarian carcinoma Ca 125, D-dimer, TPA, Ca 19-9, and CEA were investigated as tumour markers. Specificity (control group 61 gynaecologic patients with benign diseases) and sensitivity were compared in sensitivity-specificity diagrams (receiver operating characteristic curves) for different clinical tumour situations (preoperative, S0-S3). Applying a limit value of normal range, indicated in parentheses, the specificity of Ca 125 (greater than 65 mu/ml) amounts to 100%, D-dimer (greater than 700 ng/ml) 100%, TPA (greater than 120 mu/ml) 90%, CEA (greater than 5 ng/ml) 96%, Ca 19-9 (greater than 37 mu/ml) 98%. In the same sequence, sensitivity values came to 91%, 82%, 65%, 8% and 19% in manifest tumour situations. Antigen-concentration levels and frequency of pathological values depend on the degree of tumour disease. The results of seroimmunodiagnostic methods correlate with the clinical tumour situation: In 11 of 12 cases clinical tumour progression or relapse were accompanied by increasing concentrations of Ca 125 and D-dimer. In 21 cases of second-look laparotomies, tumour marker values in the normal range were often found not to be conclusive for diagnosing a tumour-free situation. The predictive value for true negative results amounted to only 18%. Immunohistochemical investigations and plasma-ascites diffusion ratios of antigens indicate that enrichment occurs in ascites. Fibrin deposition often surrounds tumour plugs and is found in interstitional tissue, whereas Ca 125 is expressed mainly at tumour cell surface. The histochemical image reflects fibrin as a tumour surrounding antigen and Ca 125 as a tumour-originated antigen. Clinical relevant serodiagnostic methods for ovarian cancer are brought about by the monoclonal detection of the investigated antigens.(ABSTRACT TRUNCATED AT 400 WORDS)