EB病毒感染与血管生成在胃癌组织芯片中的关系

Correlation between Epstein-Barr virus infection and tumor angiogenesis in patients with gastric carcinoma

目的:探讨EB病毒(Epstein-Barr virus,EBV)感染相关胃癌的构成比,其淋巴结转移癌的感染状况、临床病理特征及与血管生成的关系.方法:用原位杂交法检测胃癌组织中EBV编码的小RNA(EBERs),分析EB病毒相关胃癌的病理形态、患者年龄、性别、淋巴结转移状况等临床特征;用免疫组织化学EnVision法检测血管生成(即血管内皮生长因子(vascular endothelial growth factor,VEGF)蛋白的表达水平,分析EBV和血管生成在胃癌的表达与患者淋巴结转移状态、Lauren's分型等的关系及其相互关系.结果:486例胃癌患者中检测出感染EB病毒者(n=18,3.7%).该病毒位于肿瘤细胞核内;14例EB病毒相关胃癌患者中(77.8%)伴淋巴结转移癌,其中所有癌细胞均表达EBERs;与非EB病毒感染胃癌相比,EB病毒相关胃癌分化程度低(P<0.05),而临床TNM分期无明显差别(P>0.05);血管生成在胃癌组织中的表达率(28.2%,137/486);血管生成与患者淋巴结转移状态,TNM分期相关(P<0.05);同时,血管生成与EBV感染胃癌二者之间呈正相关(r=0.088,P=0.001).结论:EB病毒独立存在于胃癌及其淋巴结转移癌细胞核中;EB病毒相关胃癌具有独特的临床病理特征;胃癌组织中的血管生成对判断EBV感染胃癌的恶性程度和估计预后有一定意义.

AIM： To evaluate the characteristics of Epstein-Barr virus （EBV）-associated gastric cancer and to explore the correlation between EBV infection and tumor angiogenesis in patients with gastric carcinoma. METHODS： EBV infection was examined by localizing EBV-encoded small RNAs （EBERs） using in situ hybridization. Tumor angiogenesis was evaluated by examining the expression of VEGF protein using immunohistochemistry and tissue microarray technique. The association of EBV infection with clinicopathological parameters, including age, gender, tumor type, lymph node metastasis, and tumor stage, was analyzed. The correlation of VEGF expression with lymph node metastasis and Lauren’s classification was also analyzed. RESULTS： Among 486 patients, 18 showed nuclear expression of EBV. EBV staining was seen only in tumor cells. 14 of 18 patients with EBV- associated gastric cancer had regional lymph node metastasis. Of note, metastatic tumor cells in all of the involved lymph nodes contained EBV. EBER-positive gastric carcinomas tended to have lymphoid stroma （17/18） and were mostly poorly differentiated type （P0.05）. There was no significant difference in TNM stage between EBV-positive and -negative carcinomas （P0.05）. The positive rate of VEGF protein expression was 28.2% （137/486）. Angiogenesis was significantly associated with lymph node metastasis and TNM stage （both P0.05）. EBV infection was closely correlated with angiogenesis （r = 0.119, P = 0.009）. CONCLUSION： EBV is present exclusively in gastric cancer cells and tumor cells in all of the lymph nodes involved. EBV-positive gastric cancer has distinct clinicopathological features. Angiogenesis may be a good predictor of metastasis and prognosis of gastric carcinoma in patients with EBV-associated gastric cancer.