Dorn, J; Harbeck, N; Kates, R; Gkazepis, A; Scorilas, A; Soosaipillai, A; Diamandis, E; Kiechle, M; Schmalfeldt, B; Schmitt, M
Impact of expression differences of kallikrein-related peptidases and of uPA and PAI-1 between primary tumor and omentum metastasis in advanced ovarian cancer.
Primary tumor levels of serine proteases of the kallikrein-related peptidases (KLK) family as well as urokinase-type plasminogen activator (uPA) and its inhibitor PAI-1 impact disease course in ovarian cancer. The changes in levels of these factors from primary tumor to omentum metastasis ('level differentials') could thus be associated with metastastic processes.Protein levels of seven tissue KLK (KLK5-8, 10, 11, 13), uPA, and PAI-1 were determined in extracts of primary tumor tissue and corresponding omentum metastasis of 54 ovarian cancer patients.Higher level differentials of KLK5-8, 10-11, and uPA were associated with residual tumor>10 mm. Residual tumor and larger level differentials of KLK5-7, 10, and uPA were associated with disease progression in the whole cohort. Remarkably, level differentials of KLK5-8 and 10-11 strongly impacted disease progression even in patients with residual tumor mass<=10 mm; hence, the observed impact of level differentials in KLK5-7 and 10 on disease progression was not simply attributable to their association with surgical success.Since they impact both surgical outcome and survival in advanced ovarian cancer, measurement of level differentials could support clinical decisions on surgical and systemic therapy or help in patient selection for novel targeted therapies.