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Prognostic Value of the Human Kallikrein Gene 15 Expression in Ovarian Cancer

George M. Yousef, Andreas Scorilas, Dionyssios Katsaros, Stefano Fracchioli, Lisa Iskander, Carla Borgono, Irene A. Rigault de la Longrais, Manuela Puopolo, Marco Massobrio, Eleftherios P. Diamandis

From the Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, and Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada; National Center for Scientific Research "Demokritos," Athens, Greece; and Department of Obstetrics and Gynecology, Gynecologic Oncology Unit, University of Turin, and Department of Pathology, S. Anna Hospital, Turin, Italy.

Address reprint requests to Eleftherios P. Diamandis, MD, Mount Sinai Hospital, Department of Pathology and Laboratory Medicine; 600 University Ave, Toronto, Ontario M5G 1X5, Canada; email: ediamandis{at}mtsinai.on.ca.

Purpose: KLK15 is a newly cloned human kallikrein gene. Many kallikreins were found to be differentially expressed in ovarian cancer. Like other kallikreins, KLK15 is regulated by steroid hormones in cancer cell lines. KLK15 is upregulated mainly by androgens and to a lesser extent by progestins. The purpose of this study was to examine the prognostic value of KLK15 in ovarian cancer tissues.

Materials and Methods: We studied KLK15 expression by quantitative reverse transcriptase polymerase chain reaction (RT-PCR) in 168 consecutive patients with epithelial ovarian cancer. Ten patients with benign ovarian tumors were also included in the study. An optimal cutoff point equal to the 50th percentile was defined based on the ability of KLK15 to predict progression-free survival and overall survival of the study population.

Results: KLK15 expression levels were significantly higher in cancerous tissues compared with benign tumors. Kaplan-Meier survival curves showed that KLK15 overexpression is a significant predictor of reduced progression-free survival (PFS; P < .001) and overall survival (OS; P < .009). Univariate and multivariate analyses indicate that KLK15 is an independent prognostic factor for PFS and OS. A weak positive correlation was found between KLK15 expression and serum CA-125 levels.

Conclusion: KLK15 expression, as assessed by quantitative RT-PCR, is an independent marker of unfavorable prognosis for ovarian cancer.

D.K., S.F., I.A.R., and M.P. are partially supported by the Italian Association for Cancer Research. This work was also supported by a University-Industry grant from the Natural Sciences and Engineering Research Council of Canada and ONCO Therapeutics Inc.

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