title: Epstein-barr virus-positive gastric carcinoma has a distinct protein expression profile in comparison with epstein-barr virus-negative carcinoma.
abstract: OBJECTIVE
  EBV has been detected in 2-16% of gastric carcinomas. However, there is little information available about the gene expression profile of EBV-positive gastric carcinomas.
  
  
  METHODS
  EBV infection was examined using EBV-encoded small RNAs (EBERs) in situ hybridization, and 63 (5.6%) of 1127 consecutive gastric carcinomas were found to be EBV-positive. The expressions of 27 tumor-associated proteins were evaluated immunohistochemically in 63 EBV-positive gastric carcinomas and 287 EBV-negative carcinomas using the tissue array method. In addition, the genotype of EBV was investigated by PCR amplification of LMP1 (latent membrane protein 1), Epstein-Barr nuclear antigen 2 (EBNA2), and EBNA3B genes.
  
  
  RESULTS
  EBV-positive gastric carcinomas are characterized by the presence of lymphoid stroma, proximal location, and predominance in males. In comparison with EBV-negative carcinomas, EBV-positive carcinomas showed frequent loss of expression of p16, smad4, FHIT, and KAI-1 (kangai 1; P < 0.05), but retained the expression of APC (adenomatous polyposis coli), DCC (deleted in colorectal cancer), and some DNA repair proteins (P < 0.05). There was negative association between EBV infection and the expression of MUC1, MUC2, MUC5AC, p53, CEA, C-erbB2, and smad7. Using hierarchical cluster analysis, we divided EBV-positive gastric carcinomas into two clusters. Those patients with cluster 1 (42 cases) carcinomas had a better prognosis than those with cluster 2 (12 cases; P = 0.0002) or those with EBV-negative carcinomas (280 cases; P = 0.0251). Fifty-one (92.7%) of 55 EBV-positive carcinomas demonstrated the 30-bp deletion in LMP1 gene, and 53 (96.4%) of 55 cases were type 1 for EBNA2 and EBNA3B genes.
  
  
  CONCLUSIONS
  EBV-positive gastric carcinomas have a distinct protein expression profile as well as distinct clinicopathological features, as compared with EBV-negative carcinomas. The subclassification of EBV-positive carcinomas, by hierarchical cluster analysis, is significantly associated with patient survival.
authors.affiliation: Department of Pathology, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Hye Seung
authors.initials: HS
authors.lastname: Lee
authors.forename: Mee Soo
authors.initials: MS
authors.lastname: Chang
authors.forename: Han-Kwang
authors.initials: HK
authors.lastname: Yang
authors.forename: Byung Lan
authors.initials: BL
authors.lastname: Lee
authors.forename: Woo Ho
authors.initials: WH
authors.lastname: Kim
mesh_terms: D001483:Base Sequence; D016000:Cluster Analysis; D017931:DNA Primers; D005260:Female; D020869:Gene Expression Profiling; D004854:Herpesvirus 4, Human / Q000145:classification / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D017384:Sequence Deletion; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery / Q000821:virology*; D014763:Viral Matrix Proteins / Q000235:genetics
chemical_list: D017931:DNA Primers; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D009363:Neoplasm Proteins; D014763:Viral Matrix Proteins