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EBV-Associated Gastric Cancer; An In Situ Hybridization Assay on Tissue Microarray: A Multi-Region Study from Four
Maryam Abolhasani1, Ata Ollah Mohseni2, Ramin Shakeri3
1Oncopathology Research Center, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
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.
Insights
Epstein-Barr virus (EBV) was found in 2.1% of gastric cancers in Iran, predominantly in younger patients and medullary types. This low prevalence suggests regional differences in risk factors for EBV-associated gastric cancer.
Area of Science:
- Oncology
- Virology
- Gastroenterology
Background:
- Gastric cancer is a significant global health concern, ranking as the fourth leading cause of cancer deaths worldwide.
- Identifying microbial agents like Epstein-Barr virus (EBV) in gastric cancer subtypes is crucial for targeted prevention and treatment strategies.
- Iran presents diverse gastric cancer incidence rates across its provinces, making it a relevant region for epidemiological studies.
Purpose of the Study:
- To determine the frequency of Epstein-Barr virus (EBV) infection in gastric cancers across four major Iranian provinces.
- To investigate the association between EBV infection and clinicopathological characteristics of gastric tumors in the Iranian population.
Main Methods:
- Analysis of 682 gastric cancer cases using paraffin-embedded tissue blocks from various Iranian regions.
- Construction of twelve tissue microarray (TMA) blocks for efficient sample analysis.
- In situ hybridization (ISH) for Epstein-Barr virus-encoded RNA (EBER) to detect EBV presence in tumor tissues.
- Statistical evaluation using the Chi-squared test to correlate EBV-associated gastric cancer (EBVaGC) with tumor characteristics.
Main Results:
- Epstein-Barr virus (EBV) was detected in 2.1% (14 out of 682) of gastric adenocarcinoma cases.
- A significantly higher prevalence of EBV was observed in medullary gastric carcinomas (36.4%) compared to non-medullary types (0.9%) (P<0.001).
- EBV-associated gastric cancers (EBVaGC) were more common in younger patients (P=0.009) and showed a trend towards lower tumor stage (P=0.075).
Conclusions:
- The prevalence of EBV-associated gastric adenocarcinoma in Iran is low.
- This low prevalence may be attributed to regional epidemiological variations in risk factors, exposures, and a lower incidence of gastric medullary carcinomas.
- Gastric tumor heterogeneity, potentially not fully captured by TMA techniques, might also influence the observed EBV prevalence.

