胸腺瘤微卫星不稳定和杂合性缺失分析  

Analysis of microsatellite instability and loss of heterozygosity in thymoma

作　　者：邵明海[1] 陈仕林[2] 胡炜[1] 王建华[1] 王碧云[1] 

机构地区：[1]温州医学院附属台州医院放疗科,临海317000 [2]南京军区总医院胸心外科,南京210002

出　　处：《肿瘤》2008年第1期57-60,共4页Tumor

基　　金：浙江省台州市科技计划项目(编号:072KY03)

摘　　要：目的:通过检测胸腺瘤微卫星不稳定(microsatellite instability,MSI)和杂合性缺失(loss of heterozygosity,LOH)发生频率,探讨上述遗传学改变与胸腺瘤临床病理的关系。方法:选择5个微卫星多态性标记,从石蜡包埋的存档标本中选取28例胸腺瘤组织和其对应的自身正常对照组织,提取DNA后用PCR扩增,6%聚丙烯酰胺凝胶电泳(PAGE),银染显色后进行MSI和LOH分析。用免疫组织化学SP法观察EGFR、p53、Bcl-2及Ki-67在胸腺瘤中表达情况。结果:28例胸腺瘤中有11例出现MSI或LOH。在所检5个位点中D6S1708、TP53、DM、D11S988和D8S136微卫星不平衡发生率分别为21.4%(6/28)、10.7%(3/28)、14.3%(4/28)、10.7%(3/28)和0%(0/28)。D6S1708遗传学改变多为LOH(5/6),DM和D11S988位点分别仅有MSI和LOH。胸腺瘤MSI和LOH发生与患者年龄、性别、是否合并重症肌无力(myasthenia gravis,MG)、组织学分型、临床分期以及免疫组织化学EGFR、p53、Bcl-2、Ki-67表达差异均无统计学意义(P>0.05)。结论:D6S1708、TP53、DM和D11S988可以作为研究胸腺瘤微卫星的位点,微卫星不平衡可能在胸腺瘤的发生中起一定作用,但其与胸腺瘤临床病理特点的关系尚需进一步探讨。Objective ： To investigate the frequency of microsatellite instability （MSI） and loss of heterozygosity （ LOH ） in thymoma and its relationship with clinicopathological parameters. Methods：We selected 5 microsatellite polymorphism markers and extracted DNA from 28 specimens of paired thymomas/normal tissues. MSI and LOH in the specimens of thymomas and relevant pericancerous tissues were detected by polymerase chain reaction （PCR） followed by 6% polyacrylamide gel electrophoresis（PAGE） with silver staining. SP immunohistochemical method was used to assess the expressions of epithelial growth factor receptor （ EGFR）, p53, Bcl-2, and Ki-67 proteins in thymoma. Results：MSI or LOH was detected in 11 out of 28 thymoma tissues. The frequency of MSI was 21.4% （6/ 28）, 10.7% （3/28）, 14.3% （4/28）, 10.7% （3/28）, and 0% （0/28） at loci of D6S1708, TP53, DM, D11S988, and D8S136. LOH at D6S1708 （5/6） was a common genetic alteration. DM had only MSI alteration and D11S988 had only LOH alteration. There was no significant association between MSI and LOH with age, sex, with or without myasthenia gravis （ MG）, histological classification, clinical staging, and immunohistochemical staining （ EGFR, p53, Bcl-2, and Ki-67 proteins） （ P 〉 0.05 ）. Conclusion： D6S1708, TP53, DM, and D11S988 are sensitive loci for studying microsatellite DNA imbalance in thymoma. Microsatellite DNA imbalance may play a certain role in occurrence and development of thymoma, and the relationship between MSI or LOH and clinicopathological features of thymoma needs further investigation.

关 键 词：胸腺瘤 多态性 单核苷酸 微卫星不稳定 杂合子丢失 免疫组织化学 

分 类 号：R736.3[医药卫生—肿瘤]