Procollagen-derived biomarkers in malignant ascites of ovarian cancer: Independent Prognosticators for Progression-Free Interval and Survival

Objective. Matrix formation is a hallmark of solid tumor biology. Circulating antigens of structural matrix proteins should reflect this fact, yet are subject to systemic variables. We propose that if measured regionally, in a cancer-induced extravascular fluid pool such as malignant ascites of ovarian cancer, the same antigens retain their conceptual advantage as surrogate markers for tumor biology. Methods. In malignant ascites obtained at staging laparatomy of 35 women with ovarian cancer, the protein-normalized levels of the C-terminal propeptide of procollagen type I (pnPICP) and the N-terminal propeptide of procollagen type III (pnPIIINP) were determined. Using univariate and multivariate analysis, we examined these parameters, their (pnPIIINP/pnPICP) quotient, and clinical criteria (FIGO stage, age, residual tumor, histology, and tumor grade) for impact on progression-free interval and survival. Results. The absolute level of pnPIIINP was the single most powerful independent factor impacting on survival, its P value being distinctly below (P = 0.0005 vs 0.003) and its risk ratio distinctly above (15 vs 2.5) residual tumor after debulking surgery. The relative level of pnPIIINP, i.e. (pnPIIINP / pnPICP), impacted on the likelihood of recurrence even more than residual tumor. By Kaplan-Meier analysis, cutoff values for the absolute or relative pnPIIINP level significantly discriminated patients with shortened survival or progression-free interval, respectively. Conclusions. Since malignant ovarian epithelium itself forms collagen type III, and since collagen type III is a solid-phase regulator of angiogenesis, we propose that ascitic pnPIIINP is a fluid-phase indicator for angiogenic activity in ovarian cancer and thus represents a tumor virulence index.