Although at least 80% of stomach cancer is associated with
Helicobacter pylori infection, there is a subset of cancers that are
HP-negative. Epstein-Barr virus is now implicated as the cause of many
of these. The proportion of cancers caused by each depends upon the
proportion of each infection in various populations.
"EBV has been detected in the vast majority of gastric
lymphoepithelial
carcinomas and in a high proportion of lymphoepithelial carcinomas
of the lung and salivary gland. A smaller proportion of gastric
adenocarcinomas is also EBV-associated. EBV DNA has been detected
occasionally in epithelial tumours at a wide variety of other
anatomical sites. An etiological role for EBV in lymphoepithelial
and adenocarcinomas has not been conclusively established." (Epstein
Barr Virus and Kaposi's Sarcoma Herpesvirus/Human Herpesvirus 8. (IARC
Monographs on the Evaluation of Carcinogenic Risks to Humans). IARC
Monograph 70. Lyon: International Agency for Research on Cancer; 1997.)
Association of Epstein-Barr virus with undifferentiated gastric
carcinomas with intense lymphoid infiltration. Lymphoepithelioma-like
carcinoma. D Shibata, M Tokunaga, Y Uemura, E Sato, S Tanaka, LM Weiss.
American Journal of Pathology 1991 Sep;139(3):469-474. "ISH that was
performed in six of these [7] cases showed EBV genomes to be uniformly
present in the carcinoma cells and not present in the reactive lymphoid
infiltrate or normal gastric mucosa. PCR of a polymorphic EBV locus
(lymphocyte-determined membrane antigen) showed that a single genotype
was present in each gastric LELC, consistent with a clonal process.
These findings suggest that some undifferentiated gastric carcinomas
are EBV-related and that focal EBV infection occurs before
transformation."
Epstein-Barr virus-associated gastric adenocarcinoma. D Shibata, LM
Weiss. American Journal of Pathology 1992 Apr;140(4):769-774. "EBV
sequences were detected in 22 of 138 (16%) cases of typical gastric
adenocarcinoma by polymerase chain reaction and in situ hybridization
(ISH) techniques. The EBV genomes were specifically present within the
gastric carcinoma cells in an even distribution. The EBV genomes were
also present in adjacent dysplastic epithelium but were absent in
surrounding lymphocytes, other normal stromal cells, intestinal
metaplasia, and normal gastric mucosa. The EBV genomes in the infected
gastric carcinoma cells are expressed as EBV RNA was detected by ISH.
EBV was most often detected in gastric tumors from men (21%) compared
with women (3%). Thus some cases of gastric adenocarcinoma are EBV-
associated."
Association of Epstein-Barr virus with gastric carcinoma with
lymphoid stroma. K Oda, J Tamaru, T Takenouchi, A Mikata, M Nunomura, N
Saitoh, H Sarashina, N Nakajima. American Journal of Pathology 1993
Oct;143(4):1063-1071. "Epstein-Barr virus (EBV) has been detected in
lymphoepithelioma of nasopharynx and lymphoepitheliomalike carcinomas
in various organs. To clarify the association of EBV with gastric
carcinoma with lymphoid stroma, which often resembles
lymphoepithelioma, the authors examined 22 such cases by polymerase
chain reaction and in situ hybridization techniques. In 18 informative
cases, EBV DNA was detected by polymerase chain reaction in 14 (77.8%)
cases, including lymph node metastases. EBV RNA was detected within the
nuclei of carcinoma cells by in situ hybridization in all cases that
were positive by polymerase chain reaction. Infiltrating lymphocytes
and normal epithelia adjacent to carcinoma were EBV-negative. Southern
blot analysis indicated clonal proliferation of tumor cells and
episomal form of EBV. These findings suggest that EBV infection occurs
before transformation and may be related to oncogenesis of
EBV-associated gastric carcinoma."
Epstein-Barr virus in gastric carcinoma. M Tokunaga, CE Land, Y
Uemura, T Tokudome, S Tanaka, E Sato. American Journal of Pathology
1993 Nov;143(5):1250-1254. "... 999 gastric carcinomas observed in 970
consecutive cases from a large Japanese hospital. EBV involvement
occurred in 6.9 percent of lesions, a significantly lower proportion
than has been observed in a North American series. Involvement was
significantly more frequent among males, in tumors in the upper part of
the stomach, and in adenocarcinomas of the moderately differentiated
tubular and poorly differentiated solid or medullary types. Almost all
carcinomas with marked lymphoid stroma were EBV-positive. Positive
lesions were characterized by the presence of uniform hybridized
signals in almost all carcinoma cells and by their absence from
adjacent non-neoplastic tissue." [A higher prevalence of H. pylori
infection in Japan vs. North America explains the difference in
proportions -cast]
Epstein-Barr-virus-associated medullary carcinomas with lymphoid
infiltration of the stomach. Y Takano, Y Kato, H Sugano. J Cancer Res
Clin Oncol 1994;120(5):303-308. "The presence of GMCL exhibited a 2/1
male-to-female ratio and a 1/2 early-to-advanced cancer ratio,
predominantly located in the cardia and corpus of the stomach (90%).
The presence of EBV DNA could be proven in 28 out of 30 GMCL cases
(93%) by the polymerase chain reaction method, and in 27 cases (90%)
latent infection of EBV strictly limited to cancer cells was identified
by in situ hybridization with RNA using an EBV-associated small RNAs
(EBERs) probe."
Epstein-Barr virus-associated gastric carcinoma and Epstein-Barr
virus infection of the stomach. M Fukayama, Y Hayashi, Y Iwasaki, J
Chong, T Ooba, T Takizawa, M Koike, S Mizutani, M Miyaki, K Hirai. Lab
Invest 1994 Jul;71(1):73-81. "(definitely amplifiable EBV-DNA and
positive EBER1-signal in the nuclei of carcinoma cells) was found in 8
of 72 gastric carcinomas (11%). The dominant genotype of EBV was type A
(7/8), with type C (6/8), and F (8/8) restriction enzyme polymorphism,
which are the predominant type of EBV found in throat washing of the
general population in Japan."
Epstein-Barr virus in gastric carcinoma and adjacent normal gastric
and duodenal mucosa. S Shousha, YA Luqmani. J Clin Pathol 1994
Aug;47(8):695–698. 1 of 19 tumors (a lymphoepithelioma-like gastric
carcinoma) was EBV-positive. "However, scattered EBV positive cells
were seen in the normal gastric or duodenal mucosa bordering the
tumours in seven out of 11 cases," which were usual adenocarcinomas.
Monoclonal Epstein-Barr virus genomes but lack of EBV-related
protein expression in different types of gastric carcinoma. G Ott, T
Kirchner, HK Muller-Hermelink. Histopathology 1994 Oct;25(4):323-329.
Transcribed EBER sequences were found in seven (18%) of 39
gastric carcinomas.
Gastric carcinoma: monoclonal epithelial malignant cells expressing
Epstein-Barr virus latent infection protein. S Imai, S Koizumi, M
Sugiura, M Tokunaga, Y Uemura, N Yamamoto, S Tanaka, E Sato and T
Osato. Proc Natl Acad Sci USA 1994 Sep 13;91(19):9131-9135. "In 1000
primary gastric carcinomas, 70 (7.0%) contained Epstein-Barr virus
(EBV) genomic sequences detected by PCR and Southern blots. The
positive tumors comprised 8 of 9 (89%) undifferentiated
lymphoepithelioma-like carcinomas, 27 of 476 (5.7%) poorly
differentiated adenocarcinomas, and 35 of 515 (6.8%) moderately to
well-differentiated adenocarcinomas.... every keratin-positive
epithelial malignant cell expressed EBV-determined nuclear antigen 1
(EBNA1) but did not significantly express CD45+ infiltrating
leukocytes. A single fused terminal fragment was detected in each of
the EBNA1-expressing tumors, thereby suggesting that the EBV-carrying
gastric carcinomas represent clonal proliferation of cells infected
with EBV. The carcinoma cells had exclusively EBNA1 but not EBNA2, -3A,
-3B, and -3C; leader protein; and latent membrane protein 1 because of
methylation. The patients with EBV-carrying gastric carcinoma had
elevated serum EBV-specific antibodies. The EBV-specific cellular
immunity was not significantly reduced; however, the cytotoxic T-cell
target antigens were not expressed. These findings strongly suggest a
causal relation between a significant proportion of gastric carcinoma
and EBV, and the virus-carrying carcinoma cells may evade immune
surveillance."
In situ detection of Epstein-Barr virus in gastric and colorectal
adenocarcinomas. St Yuen, LP Chung, SY Leung, IS Luk, SY Chan, J Ho. Am
J Surg Pathol 1994 Nov;18(11):1158-1163. EBER was highly expressed in 7
(9.5%) of 74 gastric adenocarcinomas, while normal gastric epithelium
was EBV negative in all cases. "This pattern of positivity, together
with negative normal gastric epithelium and positive metastatic tumor,
suggested that EBV infection occurred in the dysplastic phase and that
an apparent growth advantage was conferred by the EBV infection."
Epstein-Barr virus-associated gastric adenocarcinoma in Taiwan. HJ
Harn, JY Chang, MW Wang, LI Ho, HS Lee, JH Chiang, WH Lee. Hum Pathol
1995 Mar;26(3):267-271. "Epstein-Barr virus was detected in six of 55
lesions (11%), a significantly lower proportion than has been observed
in a North American series.... These findings confirm and extend the
results of Shibata et al. They also indicate that EBV infection might
be related to oncogenesis not only in rare gastric cancers that
resemble nasopharyngeal lymphoepithelioma but also in typical gastric
adenocarcinoma."
Epstein-Barr virus infection is an early event in gastric
carcinogenesis and is independent of bcl-2 expression and p53
accumulation. ML Gulley, DR Pulitzer, PA Eagan, BG Schneider. Hum
Pathol 1996 Jan;27(1):20-27. "EBER1 was detected in 11 of 95 (12%) of
cases. When present, the virus was localized to malignant epithelial
cells and to dysplastic gastric epithelium, but was not seen in
normal-appearing gastric epithelium or intestinal metaplasia."
[Epstein-Barr associated gastric carcinoma: the genetic alteration and the expression of CD44 variant]. JM Chong, M Fukuyama. Nippon Rinsho 1997 Feb;55(2):381-385. "EBV-encoded small RNA was found in nearly all of the carcinoma cells even at the intramucosal stage."
Chong - Nippon Rinsho 1997 abstract / PubMedMorphological characteristics of Epstein-Barr virus-related early gastric carcinoma: a case-control study. J Arikawa, M Tokunaga, E Satoh, S Tanaka, CE Land. Pathol Int 1997 Jun;47(6):360-367. "A strong association between Epstein-Barr virus (EBV) and gastric carcinoma has been demonstrated by the uniform presence of EBV in all carcinoma cells, episomal monoclonality, elevated antibodies, and a unique 'lace pattern' in the mucosa...."
Arikawa - Pathol Int 1997 abstract / PubMedEpstein-Barr virus-associated gastric cancer in Russia. SA Galetsky,
VV Tsvetnov, CE Land, TA Afanasleva, NN Petrovichev, YE Gurtsevitch, M
Tokunaga. Int J Cancer 1997 Dec 10;73(6):786-789. 18 of 206 (8.7%) of
gastric carcinomas in the USSR revealed uniform EBER-1 expression
restricted to the carcinoma cells.
Frequency of Epstein-Barr virus-associated gastric adenocarcinoma in Taiwan. LL Hsieh, PJ Lin, TC Chen, JT Ou. Cancer Lett 1998 Jul 17;129(2):125-129. EBV was detected in 17 (20.7%) of 82 gastric adenocarcinomas.
Hsieh et al. Cancer Lett 1998 abstract / PubMedMicrosatellite instability, Epstein-Barr virus, mutation of type II
transforming growth factor beta receptor and BAX in gastric carcinomas
in Hong Kong. SY Leung, ST Yuen, LP Chung, KM Chu, MP Wong, FJ
Branicki, JC Ho. Br J Cancer 1999 Feb;79(3-4):582-588. Of 79 gastric
carcinomas (61 EBV negative and 18 EBV positive), "high-level MIs were
present regardless of the EBV status, and were found in a particular
clinicopathological subset of gastric carcinoma patient," namely
intestinal-type tumours (P = 0.03) and a more prominent lymphoid
infiltrate (P = 0.04).
[Detection and characterization of gastric carcinoma associated with epstein-barr virus]. VE Gurtsevich, SA Galetskii, SN Nered, EV Novikova, LS Iakovlova, ChE Land, MI Davydov, AA Klimenkov, NN Petrovichev, M Tokunaga. Vesin Ross Akad Med Nauk 1999;(3):56-59. "EBV involvement was significantly more frequent among males,... and located in the upper stomach (cardia and middle part). Most EBV-positive GCs were characterized by great lymphoid compartment involvement. The findings of the distribution of EBV-positive GCs by sex, site, and histology are similar to those in Japan; however, the detection rate of EBV-positive cases in Russia is higher than that of Japan (6.7%) and lower than that in the USA (16%)." This is probably due to lower rates of Helicobacter pylori infection in the US than in Russia or Japan. Helicobacter pylori is less associated with cancers of the gastric cardia than with other sites, and rates of cancer of the cardia have been increasing in the United States for the last 20 or so years, especially in men.
Gurtsevich - Vesin Ross Akad Med Nauk 1999 abstract / PubMedEpstein-Barr virus-associated gastric carcinoma in Mexico: analysis
of 135 consecutive gastrectomies in two hospitals. R Herrera-Goepfert,
E Reyes, M Hernandez-Avila, A Mohar, R Shinkura, C Fujiyama, S Akiba, Y
Eizuru, Y Harada, M Tokunaga. Mod Pathol 1999 Sep;12(9):873-878. 11
(8.5%) of 135 gastric carcinomas in Mexico were EBER-1-positive.
Loss of p16/CDKN2A tumor suppressor protein in gastric
adenocarcinoma is associated with Epstein-Barr virus and anatomic
location in the body of the stomach. BG Schneider, ML Gulley, P Eagan,
JC Bravo, R Mera, J Geradts. Hum Pathol 2000 Jan;31(1):45-50. "Gastric
adenocarcinomas (n = 125) were analyzed by immunohistochemistry for the
presence of p16, the CDKN2A gene product. This protein was lost in 31
of 125 cases (25%), and loss was associated with location of the tumor
in the body of the stomach (P = .001). Loss of p16 was also associated
with the presence of Epstein-Barr virus (EBV) in tumor cells as
determined by in situ hybridization (P = .022)."
Epstein-Barr virus and gastric carcinoma in Western patients:
comparison of pathological parameters and p53 expression in
EBV-positive and negative cancers. F Chapel, B Fabiani, F Davi, M
Raphael, M Tepper, G Champault, C Guettier. Histopathology 2000
Mar;36(3):252-261. In 56 gastric carcinomas, "EBERs transcripts were
detected in seven cases overall: four cases of 52 conventional
carcinomas (7. 7%) and three cases of four gastric carcinomas with
lymphoid stroma (75%)."
Epstein-Barr virus-specific antibodies in Epstein-Barr
virus-positive and -negative gastric carcinoma cases in Japan. R
Shinkura, N Yamamoto, C Koriyama, Y Shinmura, Y Eizuru, M Tokunaga. J
Med Virol 2000 Apr;60(4):411-416. In serum samples from 64 and 59
patients with EBV-positive and -negative gastric carcinomas,
respectively, and 73 healthy controls, the geometric mean titer (GMT)
of VCA-IgG was higher in EBV-positive carcinoma cases than in
EBV-negative carcinoma cases (P < 0.001).
Epstein-Barr virus-associated gastric carcinomas: relation to
Helicobacter pylori infection and genetic alterations. MS Wu, CT Shun,
CC Wu, TY Hsu, MT Lin, MC Chang, HP Wang, JT Lin. Gastroenterology 2000
Jun;118(6):1031-1038. EBV was detected in 11 (100%) LELCs and in 19
(13.7%) of 139 common GCs.
Epstein-Barr virus in gastric carcinomas with lymphoid stroma. MS
Chang, WH Kim, CW Kim, YI Kim. Histopathology 2000 Oct;37(4):309-315.
In Koreans, EBV infection was found in 30 (67%) of gastric
carcinoma with lymphoid stroma, and 10 tumours (3.4%) of non-GCLS (P
< 0.05).
Epstein-Barr virus and gastric carcinoma. K Takada. Mol Pathol 2000
Oct;53(5):255-261. Review. "The Epstein-Barr virus (EBV) is detected in
the tissue of about 10% of gastric carcinoma cases throughout the
world. In each case, 100% of carcinoma cells are infected with EBV."
"About 10% of gastric carcinomas throughout the world are monoclonal
proliferations of EBV infected carcinoma cells. Gastric carcinoma is
one of the most common carcinomas, and the worldwide occurrence of EBV
positive gastric carcinoma is estimated at more than 50 000 cases/year."
Clinicopathologic characteristics of Epstein-Barr virus-incorporated gastric cancers in Korea. MS Chang, HS Lee, CW Kim, YI Kim, WH Kim. Pathol Res Pract 2001;197(6):395-400. 5.6% of 306 consecutive gastric carcinomas were EBV+ in Korea.
Chang - Pathol Res Pract 2001 abstract / PubMedCirculating Epstein-Barr virus DNA in the serum of patients with gastric carcinoma. YM Lo, WY Chan, EK Ng, LY Chan, PB Lai, JS Tam, SC Chung. Clin Cancer Res 2001 Jul;7(7):1856-1859. EBV DNA in sera of 93-100% of EBV+ gastric carcinoma patients; also 23% of gastritis cases, versus 3.6% of apparently healthy controls.
Lo - Clin Cancer Res 2001 abstract / PubMedEpstein-Barr virus involvement is mainly restricted to lymphoepithelial type of gastric carcinoma among various epithelial neoplasms. Y Kijima, S Hokita, S Takao, M Baba, S Natsugoe, H Yoshinaka, K Aridome, T Otsuji, T Itoh, M Tokunaga, Y Eizuru, T Aikou. J Med Virol 2001 Aug;64(4):513-518. 7.3% of 313 gastric carcinomas were EBV EBER-1+ in Japan.
Kijima - J Med Virol 2001 abstract / PubMedDetection of Epstein-Barr virus in gastrectomy specimens. YA Luqmani, SO Linjawi, S Shousha. Oncol Rep 2001 Sep-Oct;8(5):995-999. 1/20 (5%) of gastric cancers were EBER+ in Kuwait.
Luqmani - Oncol Rep 2001 abstract / PubMedDistinct chromosomal aberrations in epstein-barr virus-carrying gastric carcinomas tested by comparative genomic hybridization. A Zur Hausen, NC Van Grieken, GA Meijer, MA Hermsen, E Bloemena, SG Meuwissen, JP Baak, CJ Meijer, EJ Kuipers, AJ Van Den Brule. Gastroenterology 2001 Sep;121(3):612-618. "Loss of chromosome 4p (P < 0.001) and of 11p (P < 0.02) was exclusively restricted to EBV-carrying gastric carcinomas."
zur Hausen - Gastroenterology 2001 abstract / PubMedEpstein-Barr virus-associated gastric carcinoma in Japanese Brazilians and non-Japanese Brazilians in Sao Paulo. C Koriyama, S Akiba, K Iriya, T Yamaguti, GS Hamada, T Itoh, Y Eizuru, T Aikou, S Watanabe, S Tsugane, M Tokunaga. Jpn J Cancer Res 2001 Sep;92(9):911-917.
Koriyama - Jpn J Cancer Res 2001 abstract / PubMedEpstein-Barr virus in gastric carcinoma is associated with location in the cardia and with a diffuse histology: a study in one area of Chile. A Corvalan, C Koriyama, S Akiba, Y Eizuru, C Backhouse, M Palma, J Argandona, M Tokunaga. Int J Cancer 2001 Nov 15;94(4):527-530. 16.8% of 185 cases were EBV-positive.
Corvalan - Int J Cancer 2001 abstract / PubMedEvidence of lyric infection of Epstein-Barr virus (EBV) in EBV-positive gastric carcinoma. Y Hoshikawa, Y Satoh, M Murakami, M Maeta, N Kaibara, H Ito, T Kurata, T Sairenji. J Med Virol 2002 Mar;66(3):351-359. EBV found in 14% of 21 cases.
Hoshikawa - J Med Virol 2002 abstract / PubMedThe Epstein-Barr virus-associated gastric carcinoma in Southern and
Northern China. Z Hao, C Koriyama, S Akiba, J Li, X Luo, T Itoh, Y
Eizuru, J Zou. Oncol Rep 2002 Nov-Dec;9(6):1293-1298. 9% of 198 gastric
carcinomas in Guangzhou, and 6% of 180 in Shenyang, were positive for
EBV-encoded small RNA (EBER) by ISH.
Epstein-Barr virus-associated gastric carcinoma in southern India: A
comparison with a large-scale Japanese series. J Kattoor C Koriyama, S
Akiba, T Itoh, S Ding, Y Eizuru, EK Abraham, B Chandralekha, NS Amma,
MK Nair. J Med Virol 2002 Nov;68(3):384-389. 10 / 215 (5%) gastric
cancers in Kerala, India, and 6.2% of 2011 in Japan were EBV-positive.
All 10 strains from India were subtype A.
Detection of Epstein-Barr virus in gastric carcinoma cells and
surrounding lymphocytes. K Oda, K Koda, N Takiguchi, M Nunomura, K
Seike, M Miyazaki. Gastric Cancer 2003;6(3):173-178. "EBV was detected
in 5.2% of gastric carcinomas and in 24.7% of infiltrating lymphocytes
by the ISH method. The high positive rate (21.6%) by the PCR method
corresponds to the presence of the EBV genome in surrounding
lymphocytes."
Epstein-Barr virus (EBV) and gastric carcinoma in Malaysian
patients. N Karim, G Pallesen. Malays J Pathol 2003 Jun;25(1):45-47.
Five of 50 gastric carcinomas showed EBER intranuclear positivity in
all tumour cells.
Epstein-Barr virus-associated gastric carcinoma in Cali, Colombia. E
Carrascal, C Koriyama, S Akiba, O Tamayo, T Itoh, Y Eizuru, F Garcia, M
Sera, G Carrasquilla, MB Piazuelo, L Florez, JC Bravo. Oncol Rep 2003
Jul-Aug;10(4):1059-1062. 23 of 178 (13%) consecutive gastric carcinoma
cases were EBV-positive.
Epstein-barr virus-positive gastric carcinoma has a distinct protein
expression profile in comparison with epstein-barr virus-negative
carcinoma. HS Lee, MS Chang, HK Yang, BL Lee, WH Kim. Clin Cancer Res
2004 Mar 1;10(5):1698-1705. 63 (5.6%) of 1127 consecutive gastric
carcinomas were EBV-positive. "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."
Detection of Epstein-Barr virus by PCR and expression of LMP1, p53,
CD44 in gastric cancer. MA Lee, YS Hong, JH Kang, KS Lee, JY You, KY
Lee, CH Park. Korean J Intern Med 2004 Mar;19(1):43-47. "EBV was
detected in 4 of 40 cases (10%). In 1 of 4 EBV-positive cases, EBV was
also detected in a metastatic lymph node."
[Adenocarcinomas of the stomach and distal esophagus. Incidence and phenotypic characteristics of EBV-associated cases in the Lyons area, France.] R Kerroucha, V Hervieu, ML Chambonniere, F Mege-Lechevallier, G Poncet, J Boulez, P Taniere, JY Scoazec. Ann Pathol 2004 Jun;24(3):228-235. 5 / 85 gastric adenocarcinomas (5.8%) were found by in situ hybridization (EBER-1 and -2) and immunohistochemistry (LMP1 and EBNA-1).
Kerroucha - Ann Pathol 2004 abstract / PubMed[Expression of Epstein-Barr virus genes in EBV-associated gastric
carcinoma] Y Wang, B Luo, P Zhao, BH Huang. Ai Zheng 2004
Jul;23(7):782-787. 13 EBV positive samples in 185 gastric carcinomas
(7.03%); no corresponding para-carcinomas were positive.
Histology-specific gender, age and tumor-location distributions of
Epstein-Barr virus-associated gastric carcinoma in Japan. C Koriyama, S
Akiba, A Corvalan, E Carrascal, T Itoh, R Herrera-Goepfert, Y Eizuru, M
Tokunaga. Oncol Rep 2004 Sep;12(3):543-547. "EBV-GCs accounted for 4.5%
and 6.1% of 1,088 intestinal-type and 830 diffuse-type gastric
carcinomas, respectively. Both intestinal- and diffuse-type EBV-GCs
showed male predominance, but the observed gender difference was
statistically significant only in diffuse-type carcinomas (P<0.001)."
Epstein-Barr virus infection and gastric carcinoma in Sao Paulo
State, Brazil. LF Lopes, MM Bacchi, D Elgui-de-Oliveira, SG Zanati, M
Alvarenga, CE Bacchi. Braz J Med Biol Res 2004 Nov;37(11):1707-1712.
"EBV infection was found in 6 of 53 (11.32%) gastric carcinomas, mostly
from male patients (66.7%), with a mean age of 59 years old. Most
EBV-positive tumors were in gastric antrum. Two EBV-positive tumors
(33.3%) were conventional adenocarcinomas, whereas four (66.7%) were
classified as lymphoepithelioma-like carcinomas."
Epstein-Barr virus-associated gastric carcinoma in Papua New Guinea.
J Morewaya, C Koriyama, S Akiba, D Shan, T Itoh, Y Eizuru. Oncol Rep
2004 Nov;12(5):1093-1098. 2 out of 150 gastric cancers were positive
for EBER.
Expression of Epstein-Barr virus genes in EBV-associated gastric
carcinomas. B Luo, Y Wang, XF Wang, H Liang, LP Yan, BH Huang, P Zhao.
World J Gastroenterol 2005 Feb 7;11(5):629-633. 11 / 172 (6.39%)
gastric carcinoma tissues were EBV-positive by PCR-Southern blotting
and ISH. No corresponding para-carcinoma tissues were positive (chi(2)
= 9.0909, P = 0.0026).
Epstein-Barr virus-associated gastric carcinoma: Evidence of
age-dependence among a Mexican population. R Herrera-Goepfert, S Akiba,
C Koriyama, S Ding, E Reyes, T Itoh, Y Minakami, Y Eizuru. World J
Gastroenterol 2005 Oct 21;11(39):6096-6103. In 330 consecutive,
non-selected, primary gastric carcinomas, EBER-1 was detected in 24
(7.3%) cases (male/female ratio: 1.2/1).
Correlation of Epstein-Barr virus and its encoded proteins with
Helicobacter pylori and expression of c-met and c-myc in gastric
carcinoma. B Luo, Y Wang, XF Wang, Y Gao, BH Huang, P Zhao. World J
Gastroenterol 2006 Mar 28;12(12):1842-1848. "The positive rate of H
pylori and EBV in 185 gastric carcinomas was 59.45% (110/185) and 7.03%
(13/185) respectively... The positivity of H pylori in EBV-associated
and EBV-negative gastric carcinomas was 46.15% (6/13) and
81.40%(104/172) respectively. There was no significant correlation
between EBV and H pylori infection... H pylori-positive gastric
carcinoma is predominant in antrum location, while EBVaGC has a
tendency of predominance in cardia/body location."
Association of a distinctive strain of Epstein-Barr virus with
gastric cancer. A Corvalan, S Ding, C Koriyama, E Carrascal, G
Carrasquilla, C Backhouse, L Urzua, J Argandona, M Palma, Y Eizuru, S
Akiba. Int J Cancer 2006 Apr 1;118(7):1736-1742. In tumor samples from
73 EBVaGC cases and throat washings from 329 healthy adults, "most of
the EBVaGC cases harbor a distinctive EBV strain (type "i"/XhoI +), but
in healthy donors, this strain was as common as other strains." The
odds ratio for this strain was 9.0 (95% CI 1.2-69).
Epstein-Barr virus associated gastric carcinoma: a report from Iran
in the last four decades. A Abdirad, S Ghaderi-Sohi, K Shuyama, C
Koriyama, H Nadimi-Barforoosh, S Emami, A Mosavi-Jarrahi, A Nahvijou, S
Akiba. Diagn Pathol 2007 Jul 15;2(1):25 [Epub ahead of print]. 9 (3%)
were EBV positive, out of 273 formalin fixed paraffin-embedded cases of
gastric carcinoma.
Association of Epstein-Barr virus antibody levels with precancerous
gastric lesions in a high-risk cohort. AJ Schetter, WC You, ET
Lennette, MT Gail, CS Rabkin. Cancer Sci 2008 Feb;99(2):350-354. In 183
subjects from Linqu, China, with precancerous gastric lesions (chronic
atrophic gastritis, intestinal metaplasia, and dysplasia). "Antibody
titers did not differ significantly among histological diagnoses
determined at the time of phlebotomy. However, subjects with dysplasia
at follow up had significantly higher geometric mean antibody titers
for both anti-VCA and anti-EBNA. Subjects with greater than median
antibody levels were more likely to progress between examinations,
especially in the subgroup with intestinal metaplasia at the time of
phlebotomy (odds ratios [95% confidence intervals]: 5.7 [1.6-20] for
anti-EBNA >or=1:320; 3.8 [1.0-15] for anti-VCA >or=1:640)."
Epstein-Barr Virus-Positive Gastric Carcinoma Demonstrates Frequent Aberrant Methylation of Multiple Genes and Constitutes CpG Island Methylator Phenotype-Positive Gastric Carcinoma. GH Kang, S Lee, WH Kim, HW Lee, JC Kim, M-G Rhyu, JY Ro. American Journal of Pathology. 2002 Mar;160(3):787-794. "EBV-positive GCs showed simultaneous methylation of multiple genes involved in several molecular pathways in gastric carcinogenesis, including cell cycle regulation (p16, p14, 14-3-3 sigma, and COX2), DNA repair and protection (hMLH1, MGMT, and GSTP1), cell adherence and metastasis (E-cadherin and TIMP-3), angiogenesis (THBS1), apoptosis (DAP-kinase), and signal transduction (APC, PTEN, and RASSF1A). The average number of methylated MINT loci was significantly greater in EBV-positive GCs than in EBV-negative GCs."
Kang / Am J Pathol 2002 full articleEpstein-barr virus-positive gastric carcinoma has a distinct protein
expression profile in comparison with epstein-barr virus-negative
carcinoma. HS Lee, MS Chang, HK Yang, BL Lee, WH Kim. Clin Cancer Res
2004 Mar 1;10(5):1698-1705. 63 (5.6%) of 1127 consecutive gastric
carcinomas were EBV-positive. "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."
The Epstein-Barr Virus Protein BMRF1 Activates Gastrin Transcription. EA Holley-Guthrie, WT Seaman, P Bhende, JL Merchant, SC Kenney. J Virol 2005 Jan;79(2):745-755. "Furthermore, as the EBV genome is present in up to 10% of gastric cancers, and the different forms of gastrin are growth factors for gastrointestinal epithelium, our results suggest a mechanism by which lytic EBV infection could promote the growth of gastric cells."
Holley-Guthrie - J Virology 2005 abstractRelationship between abnormality of FHIT gene and EBV infection in
gastric cancer. Y-P Xiao, C-B Han, X-Y Mao, J-Y Li, L Xu, C-S Ren, Y
Xin. World J. Gastroenterol 2005 Jun 7;11(21):3212-3216. "EBV was
detected in 5/50 (10%) gastric cancers, among which 4/5 (80%) had
aberrant transcripts of FHIT [fragile histidine triad] gene."
Down-regulation of locus-specific human lymphocyte antigen class I
expression in Epstein-Barr virus-associated gastric cancer: implication
for viral-induced immune evasion. N Dutta, A Gupta, DN Mazumder, S
Banerjee. Cancer 2006 Apr 15;106(8):1685-1693. "The current results
suggested that the establishment of EBV latent infection in gastric
tissues allows malignant cells to avoid the immune surveillance of both
cytotoxic T-lymphocytes and natural killer cells by regulating the
differential expression of HLA class I molecules. 2006 American Cancer
Society."
p73 gene promoter methylation in Epstein-Barr virus-associated
gastric carcinoma. T Ushiku, JM Chong, H Uozaki, R Hino, MS Chang, M
Sudo, BR Rani, K Sakuma, H Nagai, M Fukayama. Int J Cancer 2007 Jan
1;120(1):60-66. "Loss of p73 expression by immunohistochemistry was
specific to EBV-associated GC (11/13) compared to EBV-negative GC
(3/38), which was independent of abnormal p53 expression. With
methylation-specific polymerase chain reaction (MSP), the aberrant
methylation of p73 exon 1 was similarly specific to EBV-associated GC
(12/13), and also rare in EBV-negative GC (2/38). Bisulfite sequencing
for p73 exon 1 and its 5' region confirmed the MSP results, showing
uniform and high-density methylation in EBV-associated GC."
Oncogenic T-antigen of JC virus is present frequently in human
gastric cancers. SK Shin, MS Li, F Fuerst, E Hotchkiss, R Meyer, T Kim
2nd, A Goel, CR Boland. Cancer 2006 Aug 1;107(3):481-488. "Twenty-one
of 37 gastric cancers (57%) harbored JCV T-Ag sequences, and 13 of 37
gastric cancers (30%) contained VP-1 sequences. T-Ag sequences also
were found in adjacent nonneoplastic mucosa. In addition, JCV
regulatory region sequences were present frequently in gastric cancers
and adjacent nonneoplastic mucosa. T-Ag protein expression was found in
9 of 23 gastric cancers (39%), whereas no expression was observed in
any of the nonneoplastic tissues."
cast 03-07-08