【摘要】 目的探讨特定位点微卫星DNA序列不稳定性(MSI)及杂合性缺失(LOH)与人甲状腺癌发生、临床病理特征及预后的关系。方法选取THRA1、D2S123、D11S912、BAT-26四个位点,应用聚合酶链反应(PCR)和变性聚丙烯酰胺凝胶电泳技术,对60例人甲状腺癌患者的MSI及LOH表达情况进行研究。结果THRA1位点MSI检出频率为43.3%,D2S123为36.7%;甲状腺滤泡癌中D2S123检出率为100%,未检测到BAT-26;D18S58的检出率为26.7%;BAT-26在甲状腺癌中检出率为6.7%;LOH的检出率分别为33.3%、26.7%、23.3%和16.7%。术后随访5年,MSI/LOH阳性的甲状腺癌较阴性者生存期更长(P<0.05)。结论在2号和18号染色体中检测到微卫星阳性率较高;D2S123位点MSI与滤泡型甲状腺癌相关性有统计学意义;D18S58位点MSI的阳性率与高龄患者、晚期肿瘤密切相关;BAT-26在甲状腺癌中检出率最低。MSI/LOH导致基因组不稳定,在甲状腺肿瘤发生过程中发挥作用。MSI/LOH阳性的甲状腺癌患者较阴性者生存期更长。更多还原

【Abstract】 Objective To investigate the relationship between the microsatellite instability(MSI) and the loss of heterozygosity(LOH) in thyroid carcinoma and the occurrence,clinic pathological features and prognosis.Methods THRA1,D2S123,D11S912 and BAT-26 site point were selected and analyzed by PCR and degenerative polyacrylamide gel electrophoresis(PAGE).The expressions of MSI and LOH in 60 patients with thyroid carcinoma were measured and the patients 5-year survival rate were counted.Results The most frequent MSI was observed at THRA1 with an incidence of 43.3%(26/60),MSI on D2S123 was detected in 36.7%(22/60) of the tumor.In follicular cancer,MSI in D2S123 occurred at a frequency of 100%(12/12),0% in BAT-26 and 26.7% in D18S58.BAT-26,which was an important marker in colorectal cancer,displayed the lowest frequency of MSI in the detected thyroid tumors 6.7%(4/60).The expression rate of LOH was 33.3%(20/60),26.7%(16/60),23.3%(14/60) and 16.7%(10/60) respectively.By 5-years follow-up visit,patients with MSI/LOH-positive cancer showed better long-term survival(P=0.007).Conclusions The high frequency of MSI can be detected at both 2p and 18q loci.It is identified that there are correlations between MSI on D2S123,D18S58 chromosome and clinical pathologic characteristics.The link between MSI in D2S123 and follicular carcinoma is calculated to be statistically significant.The correlation between MSI in D18S58 and patient age,terminal tumor is significant.This finding of the low frequency of MSI in BAT-26 suggests that the biochemical defects governing the spectrum of MSI in thyroid and colorectal cancer are different. MSI/LOH leads to the instability of the genome,has the notable significance in occuring of the thyroid tumors.Patients with MSI/LOH positive cancer have better long-term survival.更多还原