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Prognostic relevance of high atonal homolog-1 expression in Merkel cell carcinoma

  • Original Article – Cancer Research
  • Published:
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Abstract

Background

It has recently been reported that atonal homolog 1 (ATOH1) gene is down-regulated in Merkel cell carcinoma (MCC) and thus may represent a tumor suppressor gene.

Objectives

We aimed to test for ATOH1 gene mutations and expression levels in MCC tissues and cell lines.

Methods

Genomic DNA isolation and amplification via PCR was successfully performed in 33 MCCs on formalin-fixed paraffin-embedded tissue and three MCC cell lines, followed by Sanger sequencing of the whole ATOH1 gene to detect genomic aberrations. ATOH1 mRNA levels were determined by RT-PCR. Immunohistochemistry of ATOH1 was performed to quantify protein expression in tumor samples and cell lines.

Results

Neither in any of the 33 MCC tissue samples nor in the three cell lines ATOH1 mutations were present. ATOH1 was expressed in all lesions, albeit at different expression levels. Univariate analysis revealed that the total immunohistology score significantly correlated with the occurrence of tumor relapse (r = 0.57; P = 0.0008). This notion was confirmed in multivariate analysis suggesting that ATOH1 expression is a potential independent predictor for tumor relapse in MCC patients (P = 0.028). MCC-related death also correlated with ATOH1 expression (r = 0.4; P = 0.025); however, ATOH1 expression did not retain its predictive value in the regression model.

Conclusions

In contrast to anecdotal reports ATOH1 expression is not lost by genetic alterations in MCC. However, protein expression of ATOH1 is increased in advanced MCC indicating that ATOH1 is involved in MCC progression.

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Acknowledgments

This work was supported by a FoRUM research grant of the Ruhr-University Bochum (FoRUM AZ: F855N2-2015). MCPyV DNA analyses were supported by the National Reference Center for Papilloma- and Polyomaviruses, Grant No. 1369-401.

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Authors and Affiliations

  1. Department of Dermatology, Skin Cancer Center, Ruhr-University Bochum, Gudrunstrasse 56, 44791, Bochum, Germany

    T. Gambichler, S. Mohtezebsade, A.-K. Höh, M. Dreißigacker, E. Stockfleth, M. Stücker & F. G. Bechara

  2. National Reference Center for Papilloma- and Polyomaviruses, Institute of Virology, University of Cologne, Cologne, Germany

    U. Wieland & S. Silling

  3. Dermatopathology Duisburg, Duisburg, Germany

    J. Schaller

  4. Department of Dermatology and Dermato-Histo-Pathology, Skin Cancer Center, Fachklinik Hornheide, Münster, Germany

    H.-J. Schulze

  5. Institute for Pathology, Mülheim/Ruhr, Germany

    F. Oellig

  6. Department of Dermatology, Venereology and Allergology, HELIOS St. Elisabeth Hospital Oberhausen, Oberhausen, Germany

    A. Kreuter

  7. Translational Skin Cancer Research, DKTK Partner Site Essen/Düsseldorf, West German Cancer Center, Dermatology, University Duisburg-Essen, Essen, Germany

    J. C. Becker

Authors
  1. T. Gambichler
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  2. S. Mohtezebsade
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  3. U. Wieland
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  4. S. Silling
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  5. A.-K. Höh
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  6. M. Dreißigacker
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  7. J. Schaller
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  8. H.-J. Schulze
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  9. F. Oellig
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  10. A. Kreuter
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  11. E. Stockfleth
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  12. M. Stücker
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  13. F. G. Bechara
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  14. J. C. Becker
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Corresponding author

Correspondence to T. Gambichler.

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All authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Gambichler, T., Mohtezebsade, S., Wieland, U. et al. Prognostic relevance of high atonal homolog-1 expression in Merkel cell carcinoma. J Cancer Res Clin Oncol 143, 43–49 (2017). https://doi.org/10.1007/s00432-016-2257-6

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  • DOI: https://doi.org/10.1007/s00432-016-2257-6

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