In
epithelial ovarian cancer, the high mortality rate is usually ascribed to late diagnosis, since these
tumors commonly lack early-warning symptoms, but
tumor-associated
biomarkers useful for prognosis or
therapy response prediction are in short supply. However, members of the
tissue kallikrein serine protease family, the
serine protease uPA and its inhibitor
PAI-1, are associated with
tumor progression of
ovarian cancer. Therefore, we used ELISA to determine uPA,
PAI-1, and
tissue kallikreins hK5-8, 10, 11, and 13 in extracts of 142 primary
tumor tissue specimens from
ovarian cancer patients and studied the strength of association between
protein expression levels of these
tumor tissue-associated factors. uPA,
PAI-1, hk5, and hk8 were related to FIGO stage; hK5 expression was higher in FIGO III/IV than in FIGO I/II patient tissues.
PAI-1 and hk5 differed significantly according to nuclear grading; expression of hK5 was higher in G3 than in G1/2
tumors. Associations between uPA,
PAI-1, and the
tissue kallikreins were weak. There were strong pairwise correlations within the cluster of
tissue kallikreins hK5, 6, 7, 8, 10, and 11, but their bivariate distributions depended on nuclear grading. These results support the notion that several
tissue kallikreins are co-expressed in
ovarian cancer patients, substantiating the existence of a
steroid hormone-driven
tissue kallikrein cascade in this disease.