Original Paper
Summary
We evaluated the rate of Epstein-Barr virus (EBV) in-
fection in gastric carcinomas of Korean patients and in-
vestigated the associations between EBV infection and
clinicopathological characteristics, the survival rates of
patients, and p53 overexpression. EBV-encoded small
RNA (EBER)-in situ hybridization and immunohisto-
chemistry for p53 protein were done in 306 consecutive
gastric carcinoma cases, of which 17 (5.6%) showed
EBV infection. Of these 17 EBV-positive cases, one
case strongly expressed p53 protein, while 98 (34%) of
285 EBV-negative cases overexpressed p53 (p < 0.05).
The EBV-positive gastric carcinomas tended to have
lymphoid stroma. They were mostly of the poorly dif-
ferentiated type, negative for p53 immunoexpression,
more prevalent in male patients, and diffuse according
to Lauren’s classification (p < 0.05). There was no sig-
nificant difference in the survival rate for the EBV sta-
tus. In conclusion, the EBV infection rate among gastric
carcinomas in Korea is similar to that ascertained in
other countries. An inverse correlation between EBV
and p53 overexpression was disclosed. Further study is
needed to find out whether or not two genetic changes
could be functionally overlapping during gastric car-
cinogenesis.
Key words: Stomach neoplasms – Human herpesvirus 4 –
Epstein-Barr virus – In situ hybridization – Protein p53
Introduction
The Epstein-Barr virus (EBV) is a ubiquitous human
herpes virus implicated in the etiology of many human
Clinicopathologic Characteristics of Epstein-Barr
Virus-Incorporated Gastric Cancers in Korea
M ee Soo Chang
1
, Hye Seung Lee
1
, Chul Woo Kim
1
, Yong Il Kim
1
,
and Woo Ho Kim
1, 2
1
Department of Pathology and
2
Cancer Research Institute, Seoul National University
College of Medicine, Seoul, Korea
Pathol. Res. Pract. 197: 395–400 (2001) 0344-0338/01/197/6-395 $15.00/0
PATHOLOGY
RESEARCH AND PRACTICE
© Urban & Fischer Verlag
http://www.urbanfischer.de/journals/prp
lymphoid [5] and epithelial malignancies. The presence
of EBV DNA in gastric carcinomas was first document-
ed in 1990 using the polymerase chain reaction [3]. As
the EBV-encoded small RNA (EBER) is considered a
unique marker of latent infection, and EBERs are found
in high concentration (10
6
–10
7
copies/cell) in EBV-as-
sociated gastric cancer cells [15], EBV infection in gas-
tric cancer is considered a latent state. There is some ev-
idence supporting the etiologic association between
EBV and gastric carcinoma in patients with EBV-posi-
tive gastric carcinoma. Firstly, in situ hybridization re-
veals that the EBV gene product is uniformly present in
all carcinoma cells [8, 24]. Secondly, Southern blot hy-
bridization of the EBV terminal repeat fragment dis-
closed that the EBV DNA in a carcinoma cell is mono-
clonal [13, 24]. Finally, there is serological evidence of
high antiviral titers, especially of EBV viral-capsid anti-
gen IgA and EBV early antigen R component IgG,
many years before the diagnosis of EBV-positive gas-
tric carcinoma [19].
The mechanism by which EBV contributes to the
carcinogenesis of the gastric mucosa is still unknown. It
has been thought that EBV-induced clonal proliferation
promotes the malignant transformation by increasing
the chance of oncogenic changes, and EBV is required
to maintain the malignant phenotype of EBV-associated
gastric malignancies [6, 14, 20, 23, 26, 31].
EBV-associated gastric carcinoma occurs worldwide,
with varying degrees of incidence in different countries.
Although there is some controversy about the EBV in-
Address for correspondence: Woo Ho Kim, Department
of Pathology, Seoul National University College of
Medicine, 28 Yongon-dong, Chongno-gu, Seoul 110-
799, Korea. Tel: +82-2-740-8269,
Fax: +82-2-765-5600, E-mail: woohokim@snu.ac.kr