Prognostic value of human kallikrein 10 expression in epithelial ovarian carcinoma

Purpose: Human kallikrein 10 (hK10; also known as the normal epithelial cel l-specific 1 gene and protein) is a secreted serine protease, which belongs to the human kallikrein family. It has been reported that hK10 is downregu lated in breast and prostate cancer cell lines and that it may function as a tumor suppressor. Recently, we developed a highly sensitive and specific immunoassay for hK10 and found that this protein is abundantly expressed in ovarian tissue. In this study, we measured quantitatively hK10 levels in o varian cancer cytosolic extracts and evaluated the prognostic value of this biomarker in ovarian cancer. Experimental Design: Specimens from eight normal ovarian tissues, eight ova rian tissues with benign disease, and 182 ovarian tumors were investigated. Results: hK10 concentration in ovarian tumor cytosols ranged from 0 to 84 n g/mg of total protein, with a median of 2.6. This median was highly elevate d in comparison with normal and benign ovarian tissues (P < 0.001). A cutof f of 1.35 ng/mg was selected to categorize tumors as hK10 high and hK10 low . With chi (2) test and Fisher's exact test, high concentration hK10 was fo und to be associated with advanced disease stage, serous histological type, suboptimal debulking, and large residual tumor (> 1 cm; all P < 0.05). hK1 0 status was additionally correlated with clinical outcome, including progr ession-free (PFS) and overall survival (OS) using the Cox model. In univari ate analysis, we found that patients with hK10 high tumors were more likely to die and relapse, in comparison with patients with hK10 low tumors (haza rds ratios for PFS and OS were 1.93 and 2.42, respectively; P < 0.05). Alth ough this correlation disappeared after the entire patient population was s ubjected to multivariate analysis, it remained significant in the subgroup of patients with stage III/IV ovarian cancer (hazards ratios for PFS and OS were 1.98 and 2.12, respectively; P < 0.05). Conclusions: Our results indicate that hK10 is a new, independent, unfavora ble prognostic marker, especially for late-stage ovarian cancer.