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Clinical Chemistry 52: 1879-1886, 2006. First published August 17, 2006; 10.1373/clinchem.2006.071456
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(Clinical Chemistry. 2006;52:1879-1886.)
© 2006 American Association for Clinical Chemistry, Inc.

Proteomics and Protein Markers

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

Shannon J. C. Shan1,2, Andreas Scorilas3, Dionyssios Katsaros4, Irene Rigault de la Longrais4, Marco Massobrio4 and Eleftherios P. Diamandis1,2,a

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

aAddress correspondence to this author at: Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, 600 University Ave., Toronto M5G 1X5, Ontario, Canada. Fax 416-586-8628; 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 up-regulated 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 outcomes [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.




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