Received on April 6, 2006
Accepted on July 18, 2006

Proteomics and Protein Markers

Unfavorable Prognostic Value of Human Kallikrein 7 Quantified by ELISA in Ovarian Cancer Cytosols

¹ Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada, and Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada
² Department of Biochemistry and Molecular Biology, University of Athens, Athens, Greece
³ Department of Obstetrics and Gynecology, Gynecologic Oncology and Breast Cancer Unit, University of Turin, Turin, Italy

^* To whom correspondence should be addressed. E-mail: ediamandis{at}mtsinai.on.ca.

Background: Human tissue kallikrein 7 (gene, KLK7; protein, hK7) is a member of the kallikrein family of secreted serine proteases. Reports indicate that in ovarian cancer, KLK7 is significantly upregulated at the mRNA level. The aim of this study was to determine whether hK7, measured quantitatively by ELISA in ovarian cancer cytosols, is a prognostic biomarker for ovarian cancer.

Methods: We used a newly developed ELISA with 2 monoclonal antibodies to quantify hK7 production in 260 ovarian tumor cytosols and correlated these data with various clinicopathologic variables and patient outcome [progression-free survival (PFS) and overall survival (OS)] over a median follow-up period of 52 months.

Results: Median (range) hK7 concentration in ovarian tumor cytosols was 2.84 (0-32.8) ng/mg of total protein. Compared with healthy and benign ovarian tissues and nonovarian tumors that metastasized to the ovary, malignant ovarian tumor cytosols highly overproduced hK7 (P <0.001). We used the median value as the cutoff value to categorize tumors as hK7-positive and hK7-negative. Women with hK7-positive tumors most frequently had advanced-stage disease, higher tumor grade (G3), suboptimal debulking, and serous or undifferentiated histotype (P <0.001). Univariate analysis showed that hK7 positivity was associated with significantly shorter PFS (P = 0.01) but not OS. Kaplan-Meier survival curves confirmed an increased risk of relapse in women with hK7-positive tumors (P = 0.009). In multivariate analysis, hK7 was not significantly associated with either PFS or OS.

Conclusions: hK7 is associated with other unfavorable characteristics of ovarian cancer, but it is not an independent prognosticator for ovarian cancer.