微卫星不稳定性与甲状腺癌的相关性研究

Experimental study of the association between the microsatellite instability and thyroid carcinoma

目的探讨特定位点微卫星DNA序列不稳定性(MSI)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30例人甲状腺癌中MSI表达情况进行研究,术后随访5年,了解预后。结果THRA1位点MSI检出频率较高,为43.3%,D2S123为36.7%;甲状腺滤泡癌中D2S123检出率为100%,没有检测到BAT-26;D18S58的检出率为26.7%;在直肠癌中高表达的BAT-26在甲状腺癌中检出率最低,为6.7%。术后随访5年,MSI阳性的甲状腺癌较阴性者生存期更长(P<0.05)。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;在直肠癌中高表达的BAT-26在甲状腺癌中检出率最低。结论MSI导致基因组不稳定,在甲状腺肿瘤发生过程中发挥作用。MSI阳性的甲状腺癌患者较阴性者生存期更长,并具有统计学意义(P<0.05)。

Objective To investigate the relationship between the Microsatellite Instability （MSI） and the clinicopathological features as well as the prognosis in patients with thyroid carcinoma. Methods The expression of MSI was analyzed by detecting THRA1, D2S123, D11S912, BAT-26 using polymerase chain reaction （PCR） in 30 cases of thyroid carcinoma and 30 cases of normal tissues, The postoperative course and survival rates were compared among patients with and without MSI, and 5 year survival rate were counted. Results The most frequent MSI was observed at THRA1 with an incidence of 43.3% （13/30）, MSI on D2S123 was detected in36.7% （11/30） of the tumors. In follicular cancer, MSI in D2S123 occurred at a frequency of 100% （6/6） with no （0%） occurrence of MSI at the nearby BAT-26 loci. MSI was detected about 26.7% （8/30） on D18S58. BAT-26, which is an important marker in colorectal cancer, displayed the lowest frequency of MSI in our panel of thyroid tumors 6.7% （2/30）. Follow-up survey 5 years after the operation, it was found that the patients with MSI-positive cancer showed longer survival period compared with those with MSI negative cancer. The high frequency of MSI can be detected at both 2p and 18q loci. The link between MSI in D2S123 and follicular carcinoma was statistically significant, and there was a significant correlation between MSI in D18S58 and patients＇ age as well as the stage of tumor. Lowest frequency of MSI in BAT-26 was found in thyroid, which is different from that in colorectal cancer. Conclusion MSI leads to the instability of the genome, which has the notable significance in the occurance of the thyroid tumors. Patients with MSI positive cancer showed longer survival period than those with MSI negative cancer.