EBV潜伏膜蛋白-1表达与鼻咽癌增殖和凋亡关系的研究

Correlation of EBV-LMP1 expression with proliferation and apoptosis of nasopharyngeal carcinoma

目的:研究鼻咽癌(nasopharyngeal carcinoma,NPC)组织中EBV基因EBER-1和LMP1的表达,凋亡相关基因Bcl-2和Bax,Fas和Fas-L,Caspase 3表达及其与p53蛋白的积聚、肿瘤细胞增殖和凋亡的关系。方法:分别用免疫组化染色、原位杂交和凋亡原位标记(TUNEL)技术研究NPC组织中EBV表达、凋亡相关基因表达、肿瘤增殖活性和凋亡活性。结果:87例NPC中,EBER1原位杂交(ISH)检出率为100％,EBV-LMP1阳性率63.2％(55/87),p53蛋白阳性率95.4％(83/87),肿瘤细胞Ki67核阳性率96.6％(84/87),鼻咽癌p53阳性强度与EBV-LMP1表达呈显著正相关(P<0.0005)。本组NPC病例Bcl-2和Bax阳性率分别为69.0％(60/87)和6.2％(57/87),Fas和Fas-L阳性率分别为87.2％(75/86)和54.7％(47/86),Caspase 3阳性率为62.1％(54/87)。NPC组织 Bcl-2的表达与Ki67的表达明显负相关(P<0.005),肿瘤细胞的增殖活性(Ki67的表达)与p53蛋白积聚显著正相关(P<0.0005)。Caspase 3表达与EBV-LMP1的表达呈负相关(P<0.001),但与Fas-L的表达呈正相关(P<O.025)。87例NPC组织凋亡指数(AI)值均数是87.5±65.5(TUNEL标记),肿瘤细胞凋亡活性与EBV-LMP1表达呈明显负相关,EBV-LMP1阳性的NPC组织AI值明显高于EBV-LMP1阴性组的AI值(P=0.0005);肿瘤细胞的凋亡与p53蛋白的积聚显著负相?

Objective: To study the expression of EBV EBER-1 and LMP1 ,p53 ,Ki67 and apopto-sis related genes of Bcl-2, Bax Fas,Fas-L and Caspase 3 , and their correlation with apoptosis and proliferation of nasopharyngeal carcinoma (NPC). Methods:Immunohistochemical staining and in situ hybridization (ISH)were used to study the expression of EBER-1 ,LMP1 ,p53,Ki67 and apoptosis related genes ,TUNEL in situ labelling was used to label the apoptosis activity of NPC. Results:Of the 87 cases NPC,all the cases were positive with EBER-1,63. 2%(55/87)of the cases were positive with EBV-LMP2.95. 4%(83/85) and 96. 6%(84/87) of the cases were positive with p53 and Ki67,p53 accumulation was significantly positively correlated to EBV-LMP1 expression and Ki67 expression in NPC. In the same group of NPC,69. 0%(60/87)and 65. 5%(57/87) were positive with Bcl-2 and Bax,87. 2% (75/86) and 54. 7%(47/86) were positive with Fas and Fas-L,and 62. l%(54/87)were positive with Caspase 3. Bcl-2 expression was closely negatively correlated to Ki67 expression in NPC. Caspase 3 expression was negatively correlated with EBV-LMP1,but was positively correlated to Fas-L expression in NPC. Of the 87 NPC,the mean apoptosis index (AI) value in 87.5±65. 5. Apoptosis index (AI)was negatively correlated with p53 accumulation and EBV-LMP1 expression in NPC. But AI was positively correlated to the expression of Fas-L and Caspase 3 in NPC. Conclusion: Our results indicated that proliferation and apoptosis of NPC could be con- trolled by complicated mechanisms. EBV-LMP1 expression in the NPC tumor may cause dysfunction of p53 tumor suppress gene,and suppress the expression of anti-apoptosis gene of Bcl-2 and apoptosis induce gene of Caspase 3 in NPC, thus inhibit apoptosis and promote proliferation of NPC tumor cells. Expression of Bcl-2 in the NPC tumor may suppress the tumor cell proliferation. Though apoptosis of NPC is positively correlated with expression of Fas-L and Caspase 3 in NPC,expression of Fas-L in NPC could not suppress apoptosis of NPC tumor,this indicates that there may be other ways to suppress NPC tumor apoptosis in NPC.