Abstract
BackgroundEpstein-Barr virus (EBV) has been shown to be associated with gastric cancer. However, inconsistent findings have been reported regarding the distribution of EBV infected cells (in normal gastric epithelium vs. intestinal metaplastic cells vs. in neoplastic cells) and the characteristics of EBV-associated gastric cancer. Lymph node positive EBV-associated gastric cancer has not been systematically studied. The aims of this study were to evaluate EBV-associated gastric cancer, to assess the distribution of EBV infected cells including all positive lymph nodes, and to define the characteristics of EBV-associated gastric cancer.DesignThe study included primary gastric cancer patients who underwent surgical resection with no preoperative treatment at M.D. Anderson Cancer Center between 1987 and 2006. Formalin-fixed paraffin-embedded tissue from these resection specimens were assessed for EBV by in situ hybridization, the gold standard for EBV detection in tissue. EBV status was analyzed along with clinicopathologic parameters including age, gender, tumor type, lymph node status, and pathologic stage of the tumor.ResultsAmong 235 patients, 12 had intranuclear expression of EBV. EBV staining was seen only in tumor cells and no detectable EBV was observed in normal gastric mucosa, intestinal metaplasia or stromal cells. Eight of 12 patients with EBV-associated gastric cancer had regional lymph node metastasis. Of note, metastatic tumor cells in all of the involved lymph nodes of these 8 cases contained EBV. The epidemiologic data showed 11 of the 12 patients with EBV-associated gastric cancer were men, ranging in age from 54 to 78 years (mean age, 60 years; median age, 62.1 years). The age distribution for non-EBV associated gastric cancer patients ranged from 21 to 93 years (mean age, 67 years; median age, 66.4 years).ConclusionOur study demonstrated that EBV is present exclusively in gastric cancer cells. The detection of EBV in tumor cells in all of the lymph nodes involved with metastatic gastric carcinoma suggests simultaneous replication of EBV and tumor cells. The predominantly male gender and relatively younger age observed for the EBV-infected gastric cancer cases suggest an association between this disease and other factors, such as life style.
Highlights
Epstein-Barr virus (EBV) has been shown to be associated with gastric cancer
Our study demonstrated that EBV is present exclusively in gastric cancer cells
The detection of EBV in tumor cells in all of the lymph nodes involved with metastatic gastric carcinoma suggests simultaneous replication of EBV and tumor cells
Summary
Epstein-Barr virus (EBV) has been shown to be associated with gastric cancer. Inconsistent findings have been reported regarding the distribution of EBV infected cells (in normal gastric epithelium vs intestinal metaplastic cells vs in neoplastic cells) and the characteristics of EBV-associated gastric cancer. Lymph node positive EBV-associated gastric cancer has not been systematically studied. The aims of this study were to evaluate EBV-associated gastric cancer, to assess the distribution of EBV infected cells including all positive lymph nodes, and to define the characteristics of EBV-associated gastric cancer. In 1990, Burke et al [1] used a polymerase chain reaction(PCR) method to detect Epstein-Barr virus (EBV) in a small group of gastric carcinoma cells that resembled cells of morphologically undifferentiated nasopharyngeal lymphoepithelioma. Anderson Cancer Center institutional review board approval was granted to investigate molecular markers relevant to gastric cancer pathogenesis in this study
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