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Large proportion of low frequency microsatellite-instability and loss of heterozygosity in pheochromocytoma and endocrine tumors detected with an extended marker panel

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Abstract

Purpose

Pheochromocytoma (PCC) is a usually benign tumor originated in the majority of patients from the adrenal medulla. Regarding sporadic forms of PCC, mechanisms of pathogenesis are largely unknown. Recently, microsatellite-instability (MSI) was discussed as genetic factor contributing to PCC development. Since microsatellite markers used for MSI detection have only been recommended for colorectal carcinoma (CRC), we established an extended marker set for MSI detection in PCC.

Methods

Twenty-two PCC patients were analyzed applying 11 microsatellite markers. Our marker set comprised the reference panel for CRC and six additional markers, which have already been described to detect MSI in tumors other than CRC. Moreover, 23 endocrine tumors with gastrointestinal origin were examined in order to test the applicability of this marker panel.

Results

Microsatellite-instability was detected in 41% of PCCs. Twenty-seven percent showed loss of heterozygosity (LOH) events affecting different chromosomal regions. Among the 23 patients with endocrine tumors, only three (one pancreatic endocrine tumor, one duodenal neuro-endocrine tumor, one hepatic metastasis of a primary tumor with unknown origin) demonstrated MSI.

Conclusions

The extended microsatellite panel is qualified to detect MSI in PCC. Nine percent of MSI-positive cases would have not been noticed by the use of the reference panel alone. PCCs are characterized by low frequency MSI pointing to failures in factors involved in DNA replication.

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Authors and Affiliations

  1. Department of General, Visceral and Transplant Surgery, University Hospital of Tübingen, Waldhörnlestrasse 22, 72072, Tübingen, Germany

    Susan Kupka, Marty Zdichavsky, Tanja Mlinar, Christine Kienzle & Alfred Königsrainer

  2. Department of Molecular Pathology, University Hospital of Tübingen, Tübingen, Germany

    Birgit Haack, Thomas Bock & Reinhard Kandolf

  3. Institute of Pathology, University Hospital of Tübingen, Tübingen, Germany

    Stefan-Martin Kroeber

Authors
  1. Susan Kupka
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  2. Birgit Haack
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  3. Marty Zdichavsky
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  4. Tanja Mlinar
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  5. Christine Kienzle
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  6. Thomas Bock
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  7. Reinhard Kandolf
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  8. Stefan-Martin Kroeber
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  9. Alfred Königsrainer
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Corresponding author

Correspondence to Susan Kupka.

Additional information

Susan Kupka and Birgit Haack have contributed equally to this work and thus share first authorship.

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Kupka, S., Haack, B., Zdichavsky, M. et al. Large proportion of low frequency microsatellite-instability and loss of heterozygosity in pheochromocytoma and endocrine tumors detected with an extended marker panel. J Cancer Res Clin Oncol 134, 463–471 (2008). https://doi.org/10.1007/s00432-007-0307-9

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  • DOI: https://doi.org/10.1007/s00432-007-0307-9

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