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
Rent the article at a discountRent now
* Final gross prices may vary according to local VAT.Get Access
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.
KeywordsGastric Cancer Cardia EBV Methylation
- EBV-infection in cardiac and non-cardiac gastric adenocarcinomas is associated with promoter methylation of p16, p14 and APC, but not hMLH1
Volume 34, Issue 3 , pp 209-214
- Cover Date
- Print ISSN
- Online ISSN
- Springer Netherlands
- Additional Links
- Author Affiliations
- 1. Institute of Pathology, University Hospital of Düsseldorf, Düsseldorf, Germany
- 4. Institute of Pathology, St. Vincentius Hospital, Karlsruhe, Germany
- 6. Institute of Pathology, St. Vincentius Hospital, Südendstrasse 37, 76137, Karlsruhe, Germany
- 2. Institute of Pathology, University Hospital of Freiburg, Freiburg, Germany
- 3. Institute of Pathology, Technical University of Munich, Munich, Germany
- 5. Institute of Pathology, Munich-Nymphenburg, Germany