Synthesis and breakdown of fibrillar collagens: concomitant phenomena in ovarian cancer

The synthesis and degradation of type I and type ill interstitial collagens releases several antigenic metabolites, whose measurement allows the metab olism of connective tissue to be evaluated under a variety of different con ditions. In this study we investigated the influence of benign and malignan t ovarian neoplasms on the metabolism of these collagens. The study populat ion comprised patients with benign (n = 53), borderline (n = 6) or malignan t (n = 36) ovarian neoplasms. We quantified the serum, cyst fluid and perit oneal/ascitic fluid concentrations of the amino-terminal propeptide of type I (PINP) and III (PIIINP) procollagens, indicators of the synthesis of typ e I and III collagen, respectively and the cross-linked carboxy-terminal te lopeptide of type I collagen (ICTP), an indicator of type I collagen degrad ation. Macrophage colony-stimulating factor 1 (CSF-1) concentration was als o assayed as its serum level is increased in ovarian cancer and CSF-1 may b e involved in the regulation of collagen metabolism. The concentration of e ach antigen was significantly higher in patients with malignant tumour than with benign neoplasm in each comparison, except for ICTP in peritoneal flu id and for CSF-I in cyst fluid. The high ascitic fluid concentration of PIN P, PIIINP or CSF-1 correlated with malignancy, and the low cyst fluid conce ntration of any of the four markers was indicative of benign tumour. Levels of CSF-I did not correlate with the levels of any of the markers of collag en turnover. The concentration of PINP in ascites was about 50 times higher and in cyst fluid about eight times higher than that in the serum from pat ients with malignant tumour, whereas the respective ratios for ICTP were on ly 2.5 and 1.3. In such patients, the ratio of ascitic fluid to serum conce ntration was also about 80-fold higher for PIIINP and about 20-fold higher for PINP than for ICTP. The different distributions of PIIINP, PINP and ICT P suggests dominance of synthetic processes or retarted elimination of PIII NP and PINP in ovarian cancer. In advanced malignancies, the accumulation o f PINP and PIIINP in abdominal space, possibly due to increased synthesis a nd/or failed resorption, may promote ascites formation. This study shows th at both accelerated synthesis and breakdown of fibrillar collagens are char acteristic of ovarian malignancy, and suggests that measurements of cyst fl uid or ascitic fluid concentrations of collagen metabolites or CSF-I could be used in the differential diagnosis of benign and malignant ovarian neopl asms.