MMP-9及TIMP-1在甲状腺癌组织及外周血中的表达及临床意义

Expression of Matrix Metalloproteinase-9 and Tissue Inhibitor of Metalloproteinase-1 in Thyroid Carcinoma Tissue and Their Concentrations in Serum

目的探讨甲状腺癌组织中基质金属蛋白酶-9(MMP-9)和组织金属蛋白酶抑制剂-1(TIMP-1)的表达,以及血清中MMP-9和TIMP-1浓度与肿瘤浸润、转移的关系。方法采用免疫组织化学SP法测定32例甲状腺癌组织、23例癌旁组织及30例良性甲状腺病变组织标本中MMP-9和TIMP-1的表达,并应用酶联免疫吸附试验(ELISA)方法检测MMP-9和TIMP-1在其中21例甲状腺癌和19例良性甲状腺病变患者外周血清中的浓度。结果MMP-9及TIMP-1在甲状腺癌组织中呈高表达(75.0%、56.3%),在癌旁组织及良性病变组织中呈低表达(30.4%、21.7%,26.7%、23.3%),P<0.05。MMP-9和TIMP-1蛋白的表达与肿瘤浸润程度、淋巴结转移和TNM分期有关(P<0.05),MMP-9蛋白表达与TIMP-1蛋白表达呈负相关(r=-0.509,P=0.003)。甲状腺癌组MMP-9和TIMP-1的血清浓度明显高于甲状腺良性疾病组(P=0.000,P=0.037)。甲状腺癌组织中MMP-9和TIMP-1蛋白表达高者相应血清中的MMP-9和TIMP-1浓度也较高(P<0.05)。结论检测甲状腺肿瘤患者病变组织中MMP-9和TIMP-1的表达情况及外周血中MMP-9和TIMP-1浓度有助于甲状腺良、恶性病变的鉴别诊断,并可作为甲状腺癌预后评估的依据之一。

Objective To explore the protein expressions of matrix metalloproteinase-9 （MMP-9） and tissue inhibitor of metalloproteinase-1 （TIMP-1）, and to investigate their relationships between their serum concentration before operation and the infiltration and metastasis of thyroid carcinoma. Methods The protein expressions of MMP-9 and TIMP-1 in 32 cases of thyroid carcinomas, 23 cases of adjacent tissues and 30 cases of benign hyperplastic lesions were measured by using immunohistochemistry. The preoperative serum concentrations of MMP-9 and TIMP-1 in 21 cases of thyroid carcinomas and 19 cases of benign hyperplastic lesions were determined by enzyme-linked immunosorbent assay. Results The positive expression rates of MMP-9 and TIMP-1 in tumor tissues were significantly higher （75.0% , 56.3% ）than those in adjacent tissues and benign hyperplastic lesions （30.4% , 21.7% ; 26.7%, 23.3%） P〈0.05. There were correlations between the expressions of MMP-9 and TIMP-1 and the local infiltrative degrees, lymph node metastasis and TNM stage （P〈0.05）. There was a negative correlation between the expression of MMP-9 and the expression of TIMP-1 （r=-0. 509, P=0. 003）. The concentration of MMP-9 in serum of thyroid carcinoma patients was （ 122.60±36.20） ng/ml, whereas TIMP- 1 was （59.44±38.65） ng/ml, both of which were significantly higher compared to those of benign group （P〈0.05）. In addition, there was a positive correlation between the expressions of MMP-9/TIMP 1 in the carcinoma tissues and their concentrations in serum （P〈0.05）. Conclusion To detection the expressions of MMP-9 and TIMP-1 in the lesion and their concentrations in the serum may not only contribute to the differential diagnosis of thyroid tumors, but may also help to predict the prognosis of the carcinoma.