Translationale Forschung in der gynäkologischen Onkologie: Serum-Tumormarker zur Früherkennung des Ovarialkarzinoms

Abstract

Ovarian cancer carries the worst prognosis among all gynaecological cancers, mainly due to the chemoresistance and the lack of an effective screening method for the detection of early stage disease. Early detection will be necessary to reduce the mortality of ovarian cancer. Since it has a low incidence, any screening method has to exhibit a specificity of 99 % and a positive predictive value of 10 %. Imaging techniques including transvaginal ultrasound evaluation have not reached this aim and, therefore, novel biomarkers in addition to the well established CA-125 may serve as early detection markers. Molecular screening methods with biostatistic evaluation have identified many novel biomarkers. Several marker panels have been evaluated so far, others are under investigation. This review summarizes the research status and presents also our translational project with regard to the actual literature. Utilizing oligonucleotide arrays, we identified candidate genes with high expression in cancer tissues as compared to normal controls. After developing an algorithm to identify secreted proteins, we found several genes, of which four (osteopontin, secretory leukoprotease inhibitor, kallikrein 10 and matrix metalloproteinase-7) together with CA-125 were evaluated in serum samples of 67 ovarian cancer patients and 130 healthy women. Different marker combinations could distinguish cancer from normal serum with 96 - 98.7 % sensitivity and 99.7 - 100 % specificity, respectively. In addition, all early stage cancer cases (n = 9) could be identified. A prospective study including a high number of early stage ovarian cancers and using additional novel biomarkers is warranted to validate the results.