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The asymptomatic nature of ovarian cancer, as well as previously encountered limitations of plasma-based assays, has hindered the development of a rapid, economical, reliable, and non-evasive screening tool. However, survivin, a member of the inhibitor of apoptosis protein (IAP) family, is found in ovarian surface epithelium of either benign ovarian disease or frank ovarian cancer, but is not seen in normal ovarian surface epithelium. In addition, overexpression of Bcl-2 and telomerase, is frequently found in neoplastic disease. Here, we report on the differential expression and detection of survivin, Bcl-2, and telomerase in the urine of women with benign and ovarian cancer compared to healthy controls by dot blot analysis. We likewise examined survivin, Bcl-2, and telomerase expression in imidazole-treated plasma samples from these same women. Imidazole treatment prevented protein saturation on nitrocellulose membranes, thereby allowing for rapid and economical plasma screening for potential clinical markers of disease. Telomerase was equally present in urine and plasma samples from all groups. None of the normal plasma samples tested positive for survivin. While 10% of women with ovarian cancer and greater than 33% of women with benign disease tested positive for plasma survivin, urine levels of survivin were similar between patients with benign and malignant disease. In contrast, twice the number of cancer patients had detectable Bcl-2 levels in their plasma than that of normal or benign disease patients. Further, greater than 53% of cancer patients had detectable levels of Bcl-2 in their urine, compared to 7% and 23% in urine from normal and benign disease patients, respectively. In conclusion, quantification of Bcl-2, survivin and other potential markers in imidazole-treated plasma and urine could significantly compliment the existing battery of markers for detection and prediction of clinical outcome for ovarian disease.

[Proc Amer Assoc Cancer Res, Volume 45, 2004]