胸腺肿瘤组织中EB病毒、细胞增殖和凋亡的检测

Detection of Epstein Barr virus, cell proliferation and apoptosis in thymic tumors

目的研究胸腺肿瘤在广州５所医院的发病情况，与ＥＢ病毒（ＥＢＶ）感染是否相关以及肿瘤细胞增殖和凋亡的等级。方法以４３例胸腺肿瘤和７例胸腺增生组织为研究对象。采用原位分子杂交检测ＥＢ病毒编码的ＥＢＥＲｓ，免疫组化ＬＳＡＢ法检测ＥＢＮＡ１、ＬＭＰ１、ＰＣＮＡ、ｂｃｌ２、和ｐ５３，原位细胞凋亡（ＴＵＮＥＬ）方法检测细胞凋亡。结果（１）胸腺疾病在广州５所医院活检中仅占００５７％，其中肿瘤占７４７％，增生１８６％。胸腺淋巴上皮瘤样癌（ＬＥＬＣ）占胸腺肿瘤的２７％。（２）在５０例胸腺标本中均未检测到ＥＢＶ编码的ＥＢＥＲｓ，ＥＢＮＡ１和ＬＭＰ１。（３）胸腺癌中呈高度增殖等级的病例（１０／２０例）明显多于胸腺瘤（０／１８例），而呈高级数凋亡等级的病例（１３／２０例）则低于胸腺瘤（１５／１８例）。（４）胸腺癌中ｐ５３蛋白积聚率（８／２０例）显著高于胸腺瘤（１／１８例）。胸腺上皮性肿瘤中ｐ５３蛋白积聚与凋亡等级密切相关。（５）Ｂｃｌ２在胸腺癌和胸腺瘤中均有不同程度的过表达。结论（１）胸腺疾病在广州地区极为少见，与ＥＢＶ感染无密切的关系；（２）胸腺癌与胸腺瘤相比其生长速度较快；（３）ｐ５３基因突变在胸腺癌的发生?

Objective To investigate the incidence of thymic tumors in Guangzhou, its association with EBV infection and the cell proliferation and apoptosis characteristics of these tumors. Methods EBV encoded small RNAs (EBERs) were detected in 43 thymic tumors and 7 thymic hyperplasia samples by use of in situ hybridization, EBNA 1, LMP 1, PCNA, bcl 2 and p53 were examined using immunohistochemical methods, cell apoptosis was evaluated by TUNEL (TdT mediated dUTP X nick end labelling) in situ cell death detection kit. Results 1. Thymic diseases only accounted for 0.057% of biopsies in the Guangzhou area. Thymic tumor and hyperplasia accounted for 74.7% and 18.6% in thymic diseases respectively. Thymic lymphoepithelimoa like carcinoma (LELC) occurred in 2.7% of thymic tumors. 2. EBV encoded products (EBERs, EBNA 1 and LMP 1) were not detected in 50 thymic disease specimens. 3. Marked proliferation (3+ 4+) grade thymomas (0/18 cases) was much lower than that of thymic carcinomas (10/20 cases), and the marked apoptic (2+ 4+) grade was higher in thymomas (15/18) than the thymic carcinomas (13/20). 4. The p53 protein accumulation rate in thymic carcinomas (8/20) was significantly higher than that of thymomas (1/18). The apoptotic grade is significantly related to p53 accumulation in thymic epithelial tumors. 5. The bcl 2 over expression could be detected both in thymomas and thymic carcinomas. Conclusions 1. Thymic diseases, including thymic LELC, is very rare in Guangzhou and is not closely associated with EBV infection. 2. Thymic carcinomas have a relatively rapid growth rate compared to thymomas. 3. p53 gene mutation may play an important role in the carcinogenesis of thymic carcinoma, and bcl 2 over expression may also be involved in the evolution of thymic epithelial tumors. 4. Wild type p53 protein may exert an apoptosis inducing function in thymic epithelial tumors, including thymomas and carcinomas, and a proliferation inhibiting function only in thymomas.