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Human Kallikrein 6 (hK6): A New Potential Serum Biomarker for Diagnosis and Prognosis of Ovarian Carcinoma

Eleftherios P. Diamandis, Andreas Scorilas, Stefano Fracchioli, Marleen van Gramberen, Henk de Bruijn, Alfthan Henrik, Antoninus Soosaipillai, Linda Grass, George M. Yousef, Ulf-Hakan Stenman, Marco Massobrio, Ate GJ van der Zee, Ignace Vergote, Dionyssios Katsaros

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," IPC, Athens, Greece; Department of Obstetrics and Gynecology, Gynecologic Oncology Unit, University of Turin, Turin, Italy; Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Leuven, Belgium; Department of Obstetrics and Gynecology, University Hospital Groningen, The Netherlands; and Department of Clinical Chemistry, Helsinki University Central Hospital, Helsinki, Finland.

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

Purpose: The discovery of new ovarian cancer biomarkers that are suitable for early disease diagnosis and prognosis may ultimately lead to improved patient management and outcomes.

Patients and Methods: We measured, by immunoassay, human kallikrein 6 (hK6) concentration in serum of 97 apparently healthy women, 141 women with benign abdominal diseases, and 146 women with histologically proven primary ovarian carcinoma. We then calculated the diagnostic sensitivity and specificity of this test and examined the association of serum hK6 concentration with various clinicopathologic variables and patient survival.

Results: Serum hK6 concentration between normal and benign disease patients was not different (mean, 2.9 and 3.1 µg/L, respectively). However, hK6 in presurgical serum of ovarian cancer patients was highly elevated (mean, 6.8 µg/L; P < .001). Serum hK6 decreased after surgery (to a mean of 3.9 µg/L) in 68% of patients. The diagnostic sensitivity of serum hK6 at 90% and 95% specificity is 52% and 47%, respectively, in the whole patient population. For early stage disease (stage I or II), sensitivity is approximately 21% to 26%. When combined with CA-125, at 90% specificity, sensitivity increases to 72% (for all patients) and to 42% in stage I or II disease. Serum hK6 concentration correlates moderately with CA-125 and is higher in patients with late-stage, higher-grade disease and in patients with serous histotype. Preoperative serum hK6 concentration is a powerful predictor of disease-free and overall survival in both univariate and multivariate analyses.

Conclusions: Serum hK6 concentration seems to be a new biomarker for ovarian carcinoma and may have value for disease diagnosis and prognosis.

Supported by the Early Detection Research Network (EDRN) of the National Cancer Institute (Grant No. 1CFAMA-10047), the Italian Association for Cancer Research (AIRC), and OncoTherapeutics Inc., Toronto, Canada. Dr. Diamandis is a Consultant of OncoTherapeutics Inc.

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