Tumor biology driven treatment selection in primary ovarian cancer

• Main Authors: Arnold, F, Margraf, D, Hoffmann, O, Dehn-Rotfelser, K von, Funke, I, Loewe, R, Burges, A, Beer, D, Werner, J, Mayer, B
• Format: Conference Proceeding
• Language: eng ; ger
• ISSN: 0016-5751; 1438-8804
• DOI: 10.1055/s-0034-1388483

Rationale: Primary ovarian cancer initially represents a chemosensitive tumor type. However, a considerable number of the patients suffer relapse following adjuvant platinum based therapy. Both, intrinsic and acquired drug resistance mechanisms are involved. In the present study various tumor biologic characteristics mediating drug resistance were elucidated and integrated in the therapeutic management of primary ovarian cancer. Patient and methods: Fresh tumor samples were obtained from 45 primary ovarian cancer patients. Frozen sections were prepared and analysed for drug resistance markers with qPCR. Leukocyte phenotypes involved in drug resistance were determined by FACS analysis. Protein markers reflecting tumor aggressiveness were detected using immunohistochemistry. Biomarker expression pattern were statistically correlated with follow up data using ANOVA. Results: The molecular profiling strongly reflected platinum resistance showing high expression levels of BRCA1, BRCA2 and FANCF and reduced expression levels of CCND1 and RPL32. Leukocyte phenotyping identified a high fraction of M2 macrophages (up to 32%) and regulatory T-cells (up to 16%). Strong proliferation activity was indicated by a high Ki67-LI (mean 41%) and the overexpression of several growth factors receptors, i.e. EGFR (mean 36%), HGF-R (mean 62%) and IGF1-R (mean 72%). The uPA protease system was strongly expressed (mean uPAR: 90%, mean uPA: 60%) indicating the infiltrative capacity of primary ovarian cancers. Conclusions: A number of tumor cell related and micromilieu related factors are involved mediating drug resistance in primary ovarian cancer. A detailed pretherapeutic characterization of the tumor biology is a prerequisite for the treatment management for the individual ovarian cancer patient.