Correlation of Epstein-Barr virus and its encoded proteins with Helicobacter pylori and expression of c-met and c-myc in gastric carcinoma

瞄准：为了调查 Epstein-Barr 病毒(EBV ) 和 EBV- 的相互关系，并且在胃的致癌作用探索他们的角色，与 Helicobacter pylori (H pylori ) 编码了蛋白质感染和表示遇见 c 并且在胃的癌的 c-myc oncogene 蛋白质。方法：185 胃的癌纸巾被聚合酶链反应(PCR ) 检测为 EBV 染色体的南部的污点和为编码 EBV 的小 RNA 1 (EBER1 ) 的原位杂交(ISH ) 。有积极 EBER1 信号的胃的癌被证实联系 EBV 的胃的癌(EBVaGC ) 。在 185 胃的癌的 H pylori 感染的地位被快速的 urease 和 PCR 估计。有积极 PCR 和 urease 的样品被定义为 H pylori 感染。表示遇见 c 并且在 EBVaGC 和匹配的 EBV 否定的胃的癌(EBVnGC ) 的纸巾的 c-myc oncogene 蛋白质被免疫组织化学检验。RT-PCR 和南部的杂交被用来检测原子抗原(EBNA ) 的表示 1 和 2，潜伏的膜蛋白质(LMP ) 1，在 EBVaGC 情况中的早基因 BARF1 和 BHRF1。结果：在 185 胃的癌的 H pylori 和 EBV 的积极的率是 59.45%(110/185 ) 并且 7.03%(13/185 ) 分别地。没有差别在在 pylori 积极的 H 和 H 之间的性别，年龄，病理学的区别，临床的阶段和淋巴节点转移被发现 pylori 否定的胃的癌。然而，在窦的 H pylori 感染的积极的率胃的癌比贲门和身体的高胃的癌。在我们的系列，年龄，病理学的区别，临床的阶段，淋巴节点转移和癌症的地点不在 EBVnGC 和 EBVaGC 之间是不同的，当在男病人的 EBV 的积极的率比女病人的显著地高时。在联系 EBV 、 EBV 否定的胃的癌的 H pylori 的确实是 46.15%(6/13 ) 并且 81.40%(104/172 ) 分别地。在 EBV 和 H pylori 感染之间没有重要关联。在表示上遇见 c 比在 EBVnGC 组在 EBVaGC 组是显著地更高的。然而，遇见 c 并且 c-myc 表示没显示出在二个组之间的有效差量。EBNA1 的抄本在所有 13 EBVaGCs 被检测，当 EBNA2 和 LMP1 mRNA 没被检测时。13 个盒子中的六个展出了 BARF1 抄本和 2 个展出 BHRF1 抄本。结论：在 EBVnGCs 的 H pylori 的确实比 EBVaGCs 的高，但是没有重要关联在 EBV 感染和 H pylori 感染之间被发现。H pylori 积极的胃的癌在窦地点是占优势的，当 EBVaGC 在贲门 / 身体地点有优势的一个趋势时。EBV 感染在 EBVaGC 与遇见 c 的反常表示然而并非与 c-myc 蛋白质被联系。在表示上遇见 c 没被 LMP1 导致。BARF1 和 BHRF1 可以通过不同小径在 EBVaGC 的肿瘤发生起重要作用。

AIM： To investigate the interrelationship of Epstein-Barr virus （EBV） and EBV- encoded proteins with Helicobacter pylori （H pylor/~ infection and the expression of c-met and c-myc oncogene proteins in gastric carcinoma, and to explore their role in gastric carcinogenesis. METHODS： One hundred and eighty-five gastric carcinoma tissues were detected by polymerase chain reaction （PCR）-Southern blot for EBV genome and in situ hybridization （ISH） for EBV-encoded small RNA 1 （EBER1）. Gastric carcinoma with positive EBER1 signals was confirmed EBV-associated gastric carcinoma （EBVaGC）. The status of Hpylori infection in 185 gastric carcinomas was assessed by rapid urease test and PCR. The samples with positive PCR and urease test were defined as H pylorl infection. The expression of c-met and c-myc oncogene proteins in tissues of EBVaGC and matched EBV-negative gastric carcinoma （EBVnGC） were examined by immunohistochemistry. RT-PCR and Southern hybridization were used to detect the expression of nuclear antigens （EBNAs） 1 and 2, latent membrane protein （LMP） 1, early genes BARF1 and BHRF1 in EBVaGC cases. RESULTS： The positive rate of H pylori and EBV in 185 gastric carcinomas was 59.45% （110/185） and 7.03% （13/185） respectively. No difference was found in sex, age, pathological differentiation, clinical stages and lymph node metastasis between H pylori-positive and H pylori-negative gastric carcinomas. However, the positive rate of H pylori infection in the antrum gastric carcinomas was higher than that of cardia and body gastric carcinomas. In our series, age, pathological differentiation, clinical stages, lymph node metastasis and location of cancer were not different between EBVnGC and EBVaGC, while the positive rate of EBV in male patients was significantly higher than that of female patients. The positivity of Hpylori in EBV-associated and EBV-negative gastric carcinomas was 46.15% （6/13） and 81.40%（104/172） respectively. There was no significant correlation between EBV and H pylori infection. The c-met overexpression was significantly higher in the EBVaGC group than in the EBVnGC group. However, c-met and c-myc expression did not show significant difference between the two groups. Transcripts of EBNA1 were detected in all 13 EBVaGCs, while both EBNA2 and LMP1 mRNA were not detected. Six of the 13 cases exhibited BARF1 transcripts and 2 exhibited BHRF1 transcripts. CONCLUSION： The positivity of H pylori in EBVnGCs is higher than that of EBVaGCs, but no significant correlation is found between EBV infection and H pylori infection. H pylori-positive gastric carcinoma is predominant in antrum location, while EBVaGC has a tendency of predominance in cardia/body location. EBV infection is associated with c-met abnormal expression but not with c-myc protein in EBVaGC. c-met overexpression is not induced by LMP1. BARF1 and BHRF1 may play important roles in the tumorigenesis of EBVaGC through different pathways.