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Molecular Characterization of 103 Ovarian Serous and Mucinous Tumors

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Pathology & Oncology Research

Abstract

The pathogenesis of ovarian carcinomas is heterogeneous, with even the same entities showing great variance. In our study we investigated the mutations of the BRAF, KRAS, and p53 genes in serous and mucinous borderline tumors and in low grade and high grade serous and mucinous tumors. The mutations of BRAF and KRAS genes have been shown in 60% of borderline and low grade (well differentiated) serous and mucinous tumors, but very rarely in high grade (moderately and poorly differentiated) carcinomas. However mutations of p53 are very common in high grade tumors and this indicates a "dualistic" model of ovarian tumorigenesis. A total of 80 serous tumors, including serous borderline, low grade and high grade tumors, and 23 mucinous tumors, including borderline and invasive tumors were analysed for BRAF and KRAS mutations using real time PCR method followed by melting point analysis. P53 mutation was investigated by immunohistochemistry. We assumed mutation of the p53 gene when 100% of tumor cells showed strong nuclear positivity. We observed differences in genetic alterations in the development of the low grade tumors and between low and high grade tumors too. In some bilateral or stage II-III cases we observed differences between the mutation status of the left and right ovarian tumors and between the primary tumor and its implants. In one case in a tumor with micropapillary pattern showing high grade nuclear atypia we could detect mutations in both KRAS and p53 genes. The majority of our mucinous ovarian tumor cases showed a KRAS mutation. We have not found mutations of the BRAF and p53 genes in these cases. We have found as have others, that there is a dualistic pathway of ovarian carcinogenesis. In the majority of cases, low grade epithelial tumors develop in a stepwise manner due to genetic alterations of the members of MAP-kinase pathway; however mutation of the p53 gene is the key event in the development of high grade tumors.

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Acknowledgements

We are indebted to Professor Charles E Connolly for reviewing and correcting the paper.

This study was supported by grants of the EEA and Norwegian Financial Mechanisms in Hungary, Development of joint Hungarian and Norwegian strategy for cancer treatment by molecular methods. (Prevention, early diagnosis and therapy) No. 107/2008/NA and the Project co-financed by the European Social Fund through the Sectoral Operational Programme Human Resources Development 2007–2013. Project title: Advanced Research through postdoctoral programmes in fundamental and clinical medical sciences. Contract Code: POSDRU/89/1.5/S/60782

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  1. Department of Surgical and Molecular Pathology, National Institute of Oncology, Ráth Gy u 7-9, 1122, Budapest, Hungary

    Ildikó Vereczkey, Orsolya Serester, Judit Dobos, Mónika Gallai, Orsolya Szakács, Zoltán Szentirmay & Erika Tóth

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  1. Ildikó Vereczkey
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  2. Orsolya Serester
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  3. Judit Dobos
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  4. Mónika Gallai
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Correspondence to Ildikó Vereczkey.

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Vereczkey, I., Serester, O., Dobos, J. et al. Molecular Characterization of 103 Ovarian Serous and Mucinous Tumors. Pathol. Oncol. Res. 17, 551–559 (2011). https://doi.org/10.1007/s12253-010-9345-8

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  • DOI: https://doi.org/10.1007/s12253-010-9345-8

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