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In Europe and the United States, ovarian cancer is currently the major cause of death from gynecological malignancy. Up to 60% ovarian cancer patients die from locally advanced disease. Nonetheless, even patients treated with optimal cytoreduction may subsequently suffer from metastatic disease. Since treatment strategies are developed to control locoregional cancer growth, it may be anticipated that more patients will die of distant metastases. The lack of early disease signals further contributes to the fact that only onefourth of ovarian cancers are identified at stage I. Ovarian cancer remains thus undetected due to late symptoms and the lack of reliable and clinically applicable screening tools. Further, the identification of new biomarkers could optimize prediction and monitoring of anticancer therapies and provide insights into ovarian cancer progression. Presence of disseminated tumor cells (DTC) in bone marrow is a common phenomenon observed in solid epithelial tumors. As shown by a multi-center analysis of bone marrow (BM) specimens from more than 4,700 patients, DTC detection at the time of breast cancer diagnosis is strongly correlated with poor clinical outcome (level-I-evidence) [1]. There is growing evidence that hematogenous tumor cell dissemination may occur in other tumors, such as prostate, colon and gynecologic malignancies. DTC, as surrogate parameter for occult hematogenous spread, are routinely detected in 22-51% ovarian cancer patients. Interestingly, ovarian metastases to the bone are only rarely observed [2], [3], [4]. Whether bone marrow serves in these patients as a temporary compartment from where persistent DTC are able to migrate, remains unclear. It has been demonstrated that dissemination of isolated tumor cells to secondary sites occurs as early as in FIGO stage I disease [4]. Single tumor cells acquire thus the potential to disseminate to extraperitoneal compartments early in the process of the disease. Of all prognostic factors, monitoring of minimal residual disease is the only one available after the tumor has been removed. Beside monitoring of tumor markers, there is currently a major effort to identify other biological markers which can be assessed with minimally invasive methods and persist beyond surgery. We previously reported on a significant correlation of positive bone marrow status with shortened relapse-free survival in ovarian cancer patients [5]. DTC persistence after completion of platinum-based chemotherapy was also found to be prognostically relevant [6]. Further, the identification of molecular biomarkers may represent excellent targets for new treatment strategies for chemoresistant

New Tumor Biomarkers in Ovarian Cancer and Its Prognostic and Clinical Relevance