Human tissue kallikrein 7, also known as human stratum corneum chymotryptic enzyme, is a member of the kallikrein family of secreted serine proteases. Previous reports show that seven KLK genes, including KLK7, are significantly up-regulated in ovarian carcinoma (OvCa) at the mRNA level. Nevertheless, few have studied hK7 protein expression in OvCa. To this end, we developed a highly sensitive and specific immunoassay and examined hK7 expression in OvCa cytosolic extracts. We conducted enzyme-linked immunosorbent assays (ELISA) using two hK7-specific monoclonal antibodies developed in-house. Specimens from 283 malignant, 52 benign, 45 non-ovarian metastatic tumors to the ovary, and 35 normal ovarian tissues were examined. Results were then statistically analyzed to evaluate the prognostic value of hK7 in OvCa. hK7 concentration in OvCa cytosols ranged from 0 to 66.2 ng/mg of total protein, with a median of 2.85. In comparison to normal, benign ovarian tissues, and non ovarian metastatic tumors, malignant OvCa cytosols highly over-express hK7 (p<0.001) (See figure). The median cutoff of 2.85 ng/mg was selected to categorize tumors as hK7 positive and hK7 negative. With χ2 test and Fisher’s exact test, hK7 positivity was found to be associated with advanced disease stage, suboptimal debulking, and large residual tumor (>1 cm) (all p<0.01). hK7 status was further correlated with clinical outcome, including progression-free (PFS) and overall survival (OS) using Kaplan Meier analysis as well as Cox regression models. We found that, in comparison to patients with hK7 negative tumors, patients with hK7 positive tumors were more likely to die and relapse (hazards ratios for PFS and OS were 1.59 and 2.43, respectively, p<0.05). Our results indicate that hK7 is a novel unfavorable prognostic marker for ovarian carcinoma.

[Proc Amer Assoc Cancer Res, Volume 47, 2006]