Epstein-Barr virus-associated gastric carcinomas: relation to H. pylori infection and genetic alterations.
OBJECTIVE
The association of Epstein-Barr virus (EBV) and gastric carcinomas (GCs) has been shown to vary among different populations and certain histological subtypes. Few studies have addressed the status of Helicobacter pylori infection and genetic alterations in these EBV-positive or -negative GCs.


METHODS
Eleven gastric lymphoepithelioma-like carcinomas (LELCs) and 139 cases of common non-LELCs were evaluated for the presence of EBV DNA using polymerase chain reaction (PCR) and RNA in situ hybridization. H. pylori infection was determined by anti-H. pylori immunoglobulin G in preoperative sera. Immunostaining for p53, c-erbB-2, and E-cadherin was performed. Microsatellite instability was analyzed by PCR using 10 primers.


RESULTS
EBV was detected in 11 (100%) LELCs and in 19 (13.7%) of 139 common GCs. Compared with EBV-negative GCs, gastric LELCs tended to have a relatively higher frequency of proximal location, diffuse histological subtype, p53 overexpression, and reduced E-cadherin expression but a lower frequency of lymph node metastasis, previous H. pylori infection, and c-erbB-2 overexpression. In contrast, no significant difference of clinicopathologic and genetic profiles was observed between EBV-positive non-LELC GCs and EBV-negative GCs. No correlation of microsatellite instability was found among these 3 subsets of GCs.


CONCLUSIONS
Dissecting clinicopathologic characteristics and infection status of EBV and H. pylori provide additional evidence of etiological and genetic heterogeneity for GC. Distinct clinicopathologic and genetic pathways exist in gastric LELCs, in which EBV may play a more important role than H. pylori infection.
Wu
M S
MS
Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
Shun
C T
CT
Wu
C C
CC
Hsu
T Y
TY
Lin
M T
MT
Chang
M C
MC
Wang
H P
HP
Lin
J T
JT
D000230:Adenocarcinoma / Q000382:microbiology* / Q000473:pathology / Q000821:virology*; D000368:Aged; D015820:Cadherins / Q000235:genetics; D004252:DNA Mutational Analysis; D020031:Epstein-Barr Virus Infections / Q000175:diagnosis* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D015967:Gene Expression Regulation, Viral; D016481:Helicobacter Infections / Q000175:diagnosis* / Q000473:pathology; D016480:Helicobacter pylori; D004854:Herpesvirus 4, Human; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D012367:RNA, Viral / Q000235:genetics; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D013274:Stomach Neoplasms / Q000382:microbiology* / Q000473:pathology / Q000821:virology*; D013624:Taiwan; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
D015820:Cadherins; D012367:RNA, Viral; D018719:Erb-b2 Receptor Tyrosine Kinases; D016159:Tumor Suppressor Protein p53; C099537:Epstein-Barr virus encoded RNA 1