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EBV-infection in cardiac and non-cardiac gastric adenocarcinomas is associated with promoter methylation of p16, p14 and APC, but not hMLH1

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An Erratum to this article was published on 01 June 2011

Abstract

Background

Epstein-Barr virus (EBV)-associated gastric carcinomas (GC) constitute a distinct clinicopathological entity of gastric cancer. In order to determine underlying distinct aberrant promoter methylation we tested cardiac and non-cardiac GC with regard to the presence of EBV.

Methods

One hundred GC were tested by RNA- in situ hybridization for the presence of EBV by EBV-encoded small RNA (EBER). Aberrant promoter methylation was investigated by methylation-specific real-time PCR for p16, p14, APC and hMLH1. P16 protein expression was assessed by immunohistochemistry.

Results

In our selected study cohort, EBER-transcripts were detected in 19.6% (18/92) of GC. EBV-positive GC revealed significantly more often gene hypermethylation of p16, p14 and APC (p < 0.0001, p < 0.0001, and p = 0.02, respectively) than EBV-negative GC. The majority of GC with p16 hypermethylation showed a p16 protein loss (22/28). In contrast, no correlation between the presence of EBV and hMLH1 hypermethylation was found (p = 0.7). EBV-positive GC showed a trend towards non-cardiac location (p = 0.06) and lower stages (I/II) according to the WHO (p = 0.05).

Conclusions

Hypermethylation of tumor suppressor genes is significantly more frequent in EBV-associated GC compared to EBV-negative GC. Our data add new insights to the role of EBV in gastric carcinogenesis and underline that EBV associated GC comprise a distinct molecular-pathologic as well as a distinct clinicopathological entity of GC.

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Acknowledgement

We thank R. Willers, Computer Center, Heinrich-Heine-University Düsseldorf for statistical analyses. The excellent technical assistance of Mrs. H. Huss and Mrs. C. Pawlik is greatly appreciated.

Author information

Author notes

  1. Helene Geddert

    Present address: Institute of Pathology, St. Vincentius Hospital, Karlsruhe, Germany

  2. Mario Sarbia

    Present address: Institute of Pathology, Munich-Nymphenburg, Germany

Authors and Affiliations

  1. Institute of Pathology, University Hospital of Düsseldorf, Düsseldorf, Germany

    Helene Geddert & Helmut E. Gabbert

  2. Institute of Pathology, University Hospital of Freiburg, Freiburg, Germany

    Axel zur Hausen

  3. Institute of Pathology, Technical University of Munich, Munich, Germany

    Mario Sarbia

  4. Institute of Pathology, St. Vincentius Hospital, Südendstrasse 37, 76137, Karlsruhe, Germany

    Helene Geddert

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  1. Helene Geddert
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Corresponding author

Correspondence to Helene Geddert.

Additional information

This paper is a reprint from ‘EBV-infection in cardiac and non-cardiac gastric adenocarcinomas is associated with promoter methylation of p16, p14 and APC, but not hMLH1, Helene Geddert, Axel zur Hausen, Helmut E. Gabbert, Mario Sarbia’ originally published in Analytical Cellular Pathology/Cellular Oncology, Volume 33, number 3–4, 2010, pp. 143–149, IOS Press.

An erratum to this article can be found at http://dx.doi.org/10.1007/s13402-011-0055-3

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Geddert, H., zur Hausen, A., Gabbert, H.E. et al. EBV-infection in cardiac and non-cardiac gastric adenocarcinomas is associated with promoter methylation of p16, p14 and APC, but not hMLH1 . Cell Oncol. 34, 209–214 (2011). https://doi.org/10.1007/s13402-011-0028-6

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