Maryam Abolhasani
1 
, Ata ollah Mohseni
2, Ramin Shakeri
3, Ali Khavanin
4, Mehrdad Khajehei
5, Abbasali Omidi
6, Bita Geramizadeh
7, Ensieh Shafigh
8, Farshad Naghshvar
9, Payam Fathizadeh
10, Leyla Taghizadehgan
11, Atoosa Gharib
12, Margaret L. Gulley
13, Sanford M. Dawsey
14, Reza Malekzadeh
3, Charles S. Rabkin
15* , Mohammad Vasei
16* 1 Oncopathology Research Center, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
2 Dr Mohseni’s Pathobiology Laboratory, Nour, Iran
3 Digestive Oncology Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran
4 Emergency Medicine Department, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
5 Shiraz Medical School, Shiraz University of Medical Sciences, Shiraz, Iran
6 Department of Pathology, Mashhad University of Medical Sciences, Mashhad, Iran
7 Department of Pathology, Transplantation Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
8 Department of Pathology, Babol University of Medical Sciences, Babol, Iran
9 Department of Pathology, Mazandaran University of Medical Sciences, Sari, Iran
10 Department of Pathology and Laboratory Medicine, Apadana Hospital, Ahvaz, Iran
11 Taghizadegan’s Pathology and Laboratory Medicine, Shiraz, Iran
12 Department of Pathology, Modarres Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
13 Department of Pathology, University of North Carolina, Chapel Hill, NC, USA
14 Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA
15 Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA
16 Gene Therapy Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran
Abstract
Background: Gastric cancer is the fourth leading cause of cancer-related deaths in the world. The identification of gastric cancer subtypes related to recognizable microbial agents may play a pivotal role in the targeted prevention and treatment of this cancer. The current study is conducted to define the frequency of Epstein-Barr virus (EBV) infection in gastric cancers of four major provinces, with different incidence rates of gastric cancers, in Iran.
Methods: Paraffin blocks of 682 cases of various types of gastric cancer from Tehran, South and North areas of Iran were collected. Twelve tissue microarray (TMA) blocks were constructed from these blocks. Localization of EBV in tumors was assessed by in situ hybridization (ISH) for EBV-encoded RNA (EBER). Chi-squared test was used to evaluate the statistical significance between EBV-associated gastric cancer (EBVaGC) and clinicopathologic tumor characteristics.
Results: Fourteen out of 682 cases (2.1%) of gastric adenocarcinoma were EBER-positive. EBER was positive in 8 out of 22 (36.4%) of medullary carcinomas and 6 out of 660 (0.9%) of non-medullary type, which was a statistically significant difference (P<0.001). The EBVaGCs were more frequent in younger age (P=0.009) and also showed a trend toward the lower stage of the tumor (P=0.075).
Conclusion: EBV-associated gastric adenocarcinoma has a low prevalence in Iran. This finding can be due to epidemiologic differences in risk factors and exposures, and the low number of gastric medullary carcinomas in the population. It may also be related to gastric tumor heterogeneity not detected with the TMA technique.