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A Multiparametric Panel for Ovarian Cancer Diagnosis, Prognosis, and Response to Chemotherapy

Authors' Affiliations: ¹ The Fred Hutchinson Cancer Research Center, Seattle, Washington; ² Department of Obstetrics and Gynecology, University of Turin, Turin, Italy; ³ Department of Pathology and Laboratory Medicine, Mount Sinai Hospital; ⁴ Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada; ⁵ Department of Biochemistry and Molecular Biology, University of Athens, Athens, Greece; and ⁶ diaDexus, Inc., South San Francisco, California

Requests for reprints: Eleftherios P. Diamandis, Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, ACDC Laboratory (RM l6-201), 60 Murray Street, Box 32, Toronto, Ontario, Canada M5T 3L9. Phone: 416-586-8443; Fax: 416-619-5521; E-mail: ediamandis{at}mtsinai.on.ca.

Purpose: Our goal was to examine a panel of 11 biochemical variables, measured in cytosolic extracts of ovarian tissues (normal, benign, and malignant) by quantitative ELISAs for their ability to diagnose, prognose, and predict response to chemotherapy of ovarian cancer patients.

Experimental Design: Eleven proteins were measured (9 kallikreins, B7-H4, and CA125) in cytosolic extracts of 259 ovarian tumor tissues, 50 tissues from benign conditions, 35 normal tissues, and 44 tissues from nonovarian tumors that metastasized to the ovary. Odds ratios and hazard ratios and their 95% confidence interval were calculated. Time-dependent receiver operating characteristic curves for censored survival data were used to evaluate the performance of the biomarkers. Resampling was used to validate the performance.

Results: Most biomarkers effectively separated cancer from noncancer groups. A composite marker provided an area under the curve of 0.97 (95% confidence interval, 0.95-0.99) for discriminating normal and cancer groups. Univariately, hK5 and hK6 were positively associated with progression. After adjusting for clinical variables in multivariate analysis, both hK10 and hK11 significantly predicted time to progression. Increasing levels of hK13 were associated with chemotherapy response, and the predictive power of hK13 to chemotherapy response was improved by a panel of five biomarkers.

Conclusions: The evidence shows that a group of kallikreins and multiparametric combinations with other biomarkers and clinical variables can significantly assist with ovarian cancer classification, prognosis, and response to platinum-based chemotherapy. In particular, we developed a multiparametric strategy for predicting ovarian cancer response to chemotherapy, comprising several biomarkers and clinical features.