Epstein-Barr virus associated gastric carcinoma: a report from Iran in the last four decades

Abstract

Background: Epstein-Barr virus has been proved to be associated with many of the human malignancy including gastric carcinoma, one of the most important human malignancies in the world. There has been no study about the presence of EBV in gastric adenocarcinoma in Iran.

Methods: We examined the presence of EBV in 273 formalin fixed paraffin-embedded cases of gastric carcinoma from Cancer institute of Tehran University, from 1969 to 2004. In situ hybridization of EBV-encoded small RNA-1 (EBER-1) was conducted. The strain of positive cases was examined by means of polymerase chain reaction and/or restriction fragment length polymorphism analysis.

Results: We found 9 (3%; 95% CI = 1-5%) EBV positive cases. The gender difference was not statisticaly significant. The proportion of EBV-GC cases in diffuse type was higher than intestinal type (OR = 0.08; 95% CI = 0.002-0.64). EBV-GC cases had no relation with age, location and invasion. Six out of 9 EBV-GC cases were born during the period between 1928 and 1930. All 9 cases were Type A. Prototype F was seen in 6 out of 8 cases. Type "i" was found in 8 cases and type I in 1 case. XhoI+ and XhoI- polymorphism accounted 6 and 3 of the cases, respectively.

Conclusion: Our study is the first to describe the frequency of EBV-GC in Iran and the Middle East, highlighting a very low prevalence with specific clinicopathologic features. The predominance of EBV-GC birth year in a fixed period, suggests that EBV infection or other events at early childhood may be related to the development of EBV-GC later in the life. The predominance of the type "i" and XhoI+ cases are contradictory to other studies in Asia and is similar to what is reported from Latin American countries.

Figure 1

A case of EBV positive gasrtric carcinoma. Moderately differentiated tubular adenocarcinoma with occasional tubul formation (A); nuclear EBER positive signal in all tumoral cells detected with in situ hybridization (B).

Figure 2

Result of southern blot hybridization for BamHI-F region. Four specimens are seen in this figure, each sample was loaded in 2 lanes with and without enzyme, respectively from left. The first specimen was not amplified in this experiment. The other three specimens were not cleaved by Bam-HI enzyme which means they are wild-type F. (+: positive control; +/enz: positive control with enzyme; -: negative control).

Figure 3

Result of southern blot hybridization for BamHI-W1/I1 region. Each sample was loaded in 2 lanes with and without enzyme, respectively from left. In sample one there is no band in the second lane which suggests that the PCR product was digested but we could not detect the fragmented bands since the original band contained small number of DNA copies, so we regarded it as type "i". Samples 2, 5, and 6 are cleaved which means they are type "i". Polymorphism of samples 3 and 4 were not determined in this experiment. (+: positive control; +/enz: positive control with enzyme; -: negative control).

Figure 4

Result of XhoI polymorphism in southern blot hybridization. Each sample was loaded in 2 lanes with and without enzyme respectively from left. The first and the second specimens are cleaved with enzyme which means they are XhoI+. The third one is XhoI-. (+: positive control; +/enz: positive control with enzyme; -: negative control).