Abstract

Background: In epithelial ovarian cancer (EOC), 15–20% of the tumors do not respond to first-line chemotherapy (paclitaxel with platinum-based therapy), and in recurrences this number increases. Our aim is to determine the feasibility of cell proliferation assays of tumor cells isolated from malignant ascites to predict in vitro chemotherapy sensitivity, and to correlate these results with clinical outcome.Materials and Methods: Ascites was collected from twenty women with advanced EOC. Cell samples were enriched for tumor cells and EOC origin was confirmed by intracellular staining of CK7, surface staining of CA125 and EpCAM, and HE4 gene expression. In vitro sensitivity to chemotherapy was determined in cell proliferation assays using intracellular ATP content as an indirect measure of cell number. In vitro drug response was quantified by calculation of the drug concentration at which cell growth was inhibited with 50%. Clinical outcome was determined using post-treatment CA125 level.Results: Cell samples of twenty patients were collected, of which three samples that failed to proliferate were excluded in the analysis (15%). Three other samples were excluded, because clinical outcome could not be determined correctly. In twelve of the fourteen remaining cases (86%) in vitro drug sensitivity and clinical outcome corresponded, while in two samples (14%) there was no correspondence.Conclusions: Our study demonstrates the feasibility of drug sensitivity tests using tumor cells isolated from ascites of advanced EOC patients. Larger observational studies are required to confirm the correlation between the in vitro sensitivity and clinical outcome.

Highlights

  • Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy worldwide [1]

  • Our study demonstrates the feasibility of drug sensitivity tests using tumor cells isolated from ascites of advanced epithelial ovarian cancer (EOC) patients

  • We identified twenty patients diagnosed with EOC and presenting with ascites, who gave consent for the study

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Summary

Introduction

Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy worldwide [1]. Standard first-line treatment for advanced EOC consists of a combination of a debulking surgery and chemotherapy, with paclitaxel and a platinum-based compound administered either intravenously (IV) or intraperitoneally (IP) [4]. In approximately 15–20% of women with EOC the tumor does not respond to first-line chemotherapy, and in recurrences this number increases due to drug resistance [5]. Ovarian cancers with BRCA germline and somatic mutations are more sensitive to www.oncotarget.com platinum-based therapy and Poly (ADP ribose) polymerase 1 (PARP)-inhibitors, and have better overall survival [7, 8]. In epithelial ovarian cancer (EOC), 15–20% of the tumors do not respond to first-line chemotherapy (paclitaxel with platinum-based therapy), and in recurrences this number increases. Our aim is to determine the feasibility of cell proliferation assays of tumor cells isolated from malignant ascites to predict in vitro chemotherapy sensitivity, and to correlate these results with clinical outcome

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