摘要
目的分析散发型甲状腺髓样癌(sporadic medullary thyroid carcinoma,SMTC)中酪氨酸激酶基因(rearranged during transfection,RET)、鼠肉瘤病毒基因同源基因(homologous to the oncogene from the harvey rat sarcoma virus,HRAS)突变和转录激活子(activating transcription factor 4,ATF4)蛋白表达的相关性及临床意义。方法应用PCR直接测序法检测SMTC(64例)、结节性甲状腺肿(55例)和正常甲状腺组织(35例)中RET、HRAS突变,免疫组化法检测ATF4表达情况。结果 SMTC中RET突变率为37.5%(24/64),其中M918T(18.8%)突变率较高,RET突变与肿瘤大小、包膜侵犯及淋巴结转移有关(P <0.05);所有病例中未检测到HRAS突变。SMTC中ATF4阳性率为43.8%(28/64)并与肿瘤大小、淋巴结转移有关(P 均<0.05),ATF4在RET突变组中阳性率25.0%(6/24)显著低于RET野生组的阳性率55.0%(22/40)。结论 SMTC中RET突变率较高并与肿瘤临床特征明显相关,而ATF4在SMTC中表达较低且与RET突变呈负相关,可能是SMTC的一个保护因子。
OBJECTIVE To analyze the correlation and clinical significance of RET, HRAS mutation and ATF4 protein expression in sporadic medullary thyroid carcinoma(SMTC). METHODS RET and HRAS mutations in SMTC(64 cases), nodular goiter(55 cases) and normal thyroid(35 cases) tissues were detected by PCR direct sequencing. The expression of ATF4 was detected by immunohistochemistry. RESULTS The RET mutation rate in SMTC was 37.5%(24/64), and M918 T(18.8%) mutation rate was higher. RET mutation was associated with tumor size, capsule invasion and lymph node metastasis(P<0.05).HRAS mutations were not detected in all cases. The positive rate of ATF4 in SMTC was 43.8%(28/64), which was related to tumor size and lymph node metastasis(all P values were<0.05). The positive rate of ATF4 in the RET mutation group[25.0%(6/24)] was significantly lower than that in the RET wild group[55.0%(22/40)]. CONCLUSION RET mutation rate is high in SMTC, and is significantly correlated with malignant characteristics of tumor.While ATF4 expression is low in SMTC, and negatively correlated with RET mutation, which may be a protective factor of SMTC.
作者
王慧
刘勤江
周海红
要巍
WANG Hui;LIU Qinjiang;ZHOU Haihong;YAO Wei(College of Life Sciences,Lanzhou University,Lanzhou,Gansu,730000,China;Department of Head and Neck Surgery,Gansu Cancer Hospital,Lanzhou,Gansu,730050,China;Department of Translational Medicine,Gansu Cancer Hospital,Lanzhou,Gansu,730050,China)
出处
《中国耳鼻咽喉头颈外科》
CSCD
2019年第7期373-377,共5页
Chinese Archives of Otolaryngology-Head and Neck Surgery
关键词
甲状腺肿瘤
聚合酶链反应
免疫组织化学
突变
酪氨酸激酶
鼠肉瘤病毒基因同源基因
转录激活子
Thyroid Neoplasms
Polymerase Chain Reaction
Immunohistochemistry
Mutation
rearranged during transfection
homologous to the oncogene from the Harveyrat sarcoma virus
activating transcription factor
