Research article

Potential predictive markers of chemotherapy resistance in stage III ovarian serous carcinomas

Lovisa Österberg¹ , Kristina Levan¹ , Karolina Partheen¹ , Ulla Delle¹ , Björn Olsson² , Karin Sundfeldt³ and György Horvath¹

¹  Department of Oncology, Institute of Clinical Sciences, University of Gothenburg, Sweden

²  School of Life Sciences, University College of Skövde, Sweden

³  Department of Obstetrics and Gynecology, Institute of Clinical Sciences, University of Gothenburg, Sweden

author email corresponding author email

BMC Cancer 2009, 9:368doi:10.1186/1471-2407-9-368

Published:	18 October 2009

Abstract

Background

Chemotherapy resistance remains a major obstacle in the treatment of women with ovarian cancer. Establishing predictive markers of chemoresponse would help to individualize therapy and improve survival of ovarian cancer patients. Chemotherapy resistance in ovarian cancer has been studied thoroughly and several non-overlapping single genes, gene profiles and copy number alterations have been suggested as potential markers. The objective of this study was to explore genetic alterations behind chemotherapy resistance in ovarian cancer with the ultimate aim to find potential predictive markers.

Methods

To create the best opportunities for identifying genetic alterations of importance for resistance, we selected a homogenous tumor material concerning histology, stage and chemotherapy. Using high-resolution whole genome array comparative genomic hybridization (CGH), we analyzed the tumor genomes of 40 fresh-frozen stage III ovarian serous carcinomas, all uniformly treated with combination therapy paclitaxel/carboplatin. Fisher's exact test was used to identify significant differences. Subsequently, we examined four genes in the significant regions (EVI1, MDS1, SH3GL2, SH3KBP1) plus the ABCB1 gene with quantitative real-time polymerase chain reaction (QPCR) to evaluate the impact of DNA alterations on the transcriptional level.

Results

We identified gain in 3q26.2, and losses in 6q11.2-12, 9p22.3, 9p22.2-22.1, 9p22.1-21.3, Xp22.2-22.12, Xp22.11-11.3, and Xp11.23-11.1 to be significantly associated with chemotherapy resistance. In the gene expression analysis, EVI1 expression differed between samples with gain versus without gain, exhibiting higher expression in the gain group.

Conclusion

In conclusion, we detected specific genetic alterations associated with resistance, of which some might be potential predictive markers of chemotherapy resistance in advanced ovarian serous carcinomas. Thus, further studies are required to validate these findings in an independent ovarian tumor series.