Original Paper

Cellular Oncology

, Volume 34, Issue 3, pp 209-214

First online:

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

  • Helene GeddertAffiliated withInstitute of Pathology, University Hospital of DüsseldorfInstitute of Pathology, St. Vincentius HospitalInstitute of Pathology, St. Vincentius Hospital Email author 
  • , Axel zur HausenAffiliated withInstitute of Pathology, University Hospital of Freiburg
  • , Helmut E. GabbertAffiliated withInstitute of Pathology, University Hospital of Düsseldorf
  • , Mario SarbiaAffiliated withInstitute of Pathology, Technical University of MunichInstitute of Pathology

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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.


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.


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).


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.


Gastric Cancer Cardia EBV Methylation