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BMC Cancer
Published in: BMC Cancer 1/2006

Open Access 01-12-2006 | Research article

Mismatch repair and treatment resistance in ovarian cancer

Authors: Jozien Helleman, Iris L van Staveren, Winand NM Dinjens, Patricia F van Kuijk, Kirsten Ritstier, Patricia C Ewing, Maria EL van der Burg, Gerrit Stoter, Els MJJ Berns

Published in: BMC Cancer | Issue 1/2006

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Abstract

Background

The treatment of ovarian cancer is hindered by intrinsic or acquired resistance to platinum-based chemotherapy. The aim of this study is to determine the frequency of mismatch repair (MMR) inactivation in ovarian cancer and its association with resistance to platinum-based chemotherapy.

Methods

We determined, microsatellite instability (MSI) as a marker for MMR inactivation (analysis of BAT25 and BAT26), MLH1 promoter methylation status (methylation specific PCR on bisulfite treated DNA) and mRNA expression of MLH1, MSH2, MSH3, MSH6 and PMS2 (quantitative RT-PCR) in 75 ovarian carcinomas and eight ovarian cancer cell lines

Results

MSI was detected in three of the eight cell lines i.e. A2780 (no MLH1 mRNA expression due to promoter methylation), SKOV3 (no MLH1 mRNA expression) and 2774 (no altered expression of MMR genes). Overall, there was no association between cisplatin response and MMR status in these eight cell lines.
Seven of the 75 ovarian carcinomas showed MLH1 promoter methylation, however, none of these showed MSI. Forty-six of these patients received platinum-based chemotherapy (11 non-responders, 34 responders, one unknown response). The resistance seen in the eleven non-responders was not related to MSI and therefore also not to MMR inactivation.

Conclusion

No MMR inactivation was detected in 75 ovarian carcinoma specimens and no association was seen between MMR inactivation and resistance in the ovarian cancer cell lines as well as the ovarian carcinomas. In the discussion, the results were compared to that of twenty similar studies in the literature including in total 1315 ovarian cancer patients. Although no association between response and MMR status was seen in the primary tumor the possible role of MMR inactivation in acquired resistance deserves further investigation.
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Metadata
Title
Mismatch repair and treatment resistance in ovarian cancer
Authors
Jozien Helleman
Iris L van Staveren
Winand NM Dinjens
Patricia F van Kuijk
Kirsten Ritstier
Patricia C Ewing
Maria EL van der Burg
Gerrit Stoter
Els MJJ Berns
Publication date
01-12-2006
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2006
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-6-201

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