Expression of Matrix Metalloproteinase-9 and Tissue Inhibitor of Metalloproteinase-1 in Thyroid Carcinoma Tissue and Their Concentrations in Serum_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

ZHANG Jianjun , LIU Zhiming

Department of Gastrointestinal and Gland Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China;

Corresponding author：

Keywords：

Thyroid carcinoma; Matrix metalloproteinase-9; Tissue inhibitor of metalloproteinase-1

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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.

Citation： ZHANG Jianjun,LIU Zhiming. Expression of Matrix Metalloproteinase-9 and Tissue Inhibitor of Metalloproteinase-1 in Thyroid Carcinoma Tissue and Their Concentrations in Serum. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2007, 14(4): 437-441. doi: Copy

1.	Takahashi Y, Kitadai Y, Bucana CD, et al. Expression of vascular endothelial growth factor and its receptor, KDR, correlates with vascularity, metastasis, and proliferation of human colon cancer [J]. Cancer Res, 1995; 55(18)∶3964.
2.	Zhang S, Li L, Lin JY, et al. Imbalance between expression of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in invasiveness and metastasis of human gastric carcinoma [J]. World J Gastroenterol, 2003; 9(5)∶899.
3.	Zeng ZS, Cohen AM, Guillem JG. Loss of basement membrane type Ⅳ collagen is associated with increased expression of metalloproteinases 2 and 9 (MMP-2 and MMP-9) during human colorectal tumorigenesis [J]. Carcinogenesis, 1999; 20(5)∶749.
4.	范松青，魏启幼，李美容. 基质金属蛋白酶及其抑制剂在乳腺癌中的表达及其临床意义 [J]. 癌症, 2003; 22(9)∶968.
5.	朱军华，陶凯雄，王国斌. TNF-α对肝癌细胞VEGF和MMP-9表达的影响 [J]. 中国普外基础与临床杂志， 2005; 12（4）∶384.
6.	Cho Mar K, Eimoto T, Tateyama H, et al. Expression of matrix metalloproteinases in benign and malignant follicular thyroid lesions [J]　. Histopathology, 2006; 48(3)∶286.
7.	Baldini E, Toller M, Graziano FM, et al. Expression of matrix metalloproteinases and their specific inhibitors in normal and different human thyroid tumor cell lines [J]. Thyroid, 2004; 14(11)∶881.
8.	佘浩清, 方唯意. 基质金属蛋白酶-9和原癌基因c-myc在甲状腺癌中的表达及其关系探讨 [J]. 中国现代医学杂志, 2005; 15(16)∶2457.
9.	Patel A, Straight AM, Mann H, et al. Matrix metalloproteinase (MMP) expression by differentiated thyroid carcinoma of children and adolescents [J]　. J Endocrinol Invest, 2002; 25(5)∶403.
10.	Maeta H, Ohgi S, Terada T. Protein expression of matrix metalloproteinases 2 and 9 and tissue inhibitors of metalloproteinase 1 and 2 in papillary thyroid carcinomas [J]. Virchows Arch, 2001; 438(2)∶121.
11.	Korem S, Resnick MB, Kraiem Z. Similar and divergent patterns in the regulation of matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of MMP-1 gene expression in benign and malignant human thyroid cells [J]. J Clin Endocrinol Metab, 1999; 84(9)∶3322.
12.	Komorowski J, Pasieka Z, Jankiewicz-Wika J, et al. Matrix metalloproteinases, tissue inhibitors of matrix metalloproteinases and angiogenic cytokines in peripheral blood of patients with thyroid cancer [J]. Thyroid, 2002; 12(8)∶655.
13.	Lin SY, Wang YY, Sheu WH. Preoperative plasma concentrations of vascular endothelial growth factor and matrix metalloproteinase 9 are associated with stage progression in papillary thyroid cancer [J]. Clin Endocrinol (Oxf), 2003; 58(4)∶513.
14.	Jumper C, Cobos E, Lox C. Determination of the serum matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) in patients with either advanced small-cell lung cancer or non-small-cell lung cancer prior to treatment [J]　. Respir Med, 2004; 98(2)∶173.
15.	Oberg A, Hoyhtya M, Tavelin B, et al. Limited value of preoperative serum analyses of matrix metalloproteinases (MMP-2,MMP-9) and tissue inhibitors of matrix metalloproteinases (TIMP-1, TIMP-2) in colorectal cancer [J]　. Anticancer Res, 2000; 20(2B)∶1085.
16.	Pasieka Z, Stepien H, Czyz W, et al. Concentration of metalloproteinase-2 and tissue inhibitor of metalloproteinase-2 in the serum of patients with benign and malignant thyroid tumours treated surgically [J]　. Endocr Regul, 2004; 38(2)∶57.

1. 　Takahashi Y, Kitadai Y, Bucana CD, et al. Expression of vascular endothelial growth factor and its receptor, KDR, correlates with vascularity, metastasis, and proliferation of human colon cancer [J]. Cancer Res, 1995; 55(18)∶3964.
2. 　 Zhang S, Li L, Lin JY, et al. Imbalance between expression of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in invasiveness and metastasis of human gastric carcinoma [J]. World J Gastroenterol, 2003; 9(5)∶899.
3. 　Zeng ZS, Cohen AM, Guillem JG. Loss of basement membrane type Ⅳ collagen is associated with increased expression of metalloproteinases 2 and 9 (MMP-2 and MMP-9) during human colorectal tumorigenesis [J]. Carcinogenesis, 1999; 20(5)∶749.
4. 　范松青，魏启幼，李美容. 基质金属蛋白酶及其抑制剂在乳腺癌中的表达及其临床意义 [J]. 癌症, 2003; 22(9)∶968.
5. 　朱军华，陶凯雄，王国斌. TNF-α对肝癌细胞VEGF和MMP-9表达的影响 [J]. 中国普外基础与临床杂志， 2005; 12（4）∶384.
6. 　Cho Mar K, Eimoto T, Tateyama H, et al. Expression of matrix metalloproteinases in benign and malignant follicular thyroid lesions [J]　. Histopathology, 2006; 48(3)∶286.
7. 　Baldini E, Toller M, Graziano FM, et al. Expression of matrix metalloproteinases and their specific inhibitors in normal and different human thyroid tumor cell lines [J]. Thyroid, 2004; 14(11)∶881.
8. 　佘浩清, 方唯意. 基质金属蛋白酶-9和原癌基因c-myc在甲状腺癌中的表达及其关系探讨 [J]. 中国现代医学杂志, 2005; 15(16)∶2457.
9. 　Patel A, Straight AM, Mann H, et al. Matrix metalloproteinase (MMP) expression by differentiated thyroid carcinoma of children and adolescents [J]　. J Endocrinol Invest, 2002; 25(5)∶403.
10. 　Maeta H, Ohgi S, Terada T. Protein expression of matrix metalloproteinases 2 and 9 and tissue inhibitors of metalloproteinase 1 and 2 in papillary thyroid carcinomas [J]. Virchows Arch, 2001; 438(2)∶121.
11. 　Korem S, Resnick MB, Kraiem Z. Similar and divergent patterns in the regulation of matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of MMP-1 gene expression in benign and malignant human thyroid cells [J]. J Clin Endocrinol Metab, 1999; 84(9)∶3322.
12. 　Komorowski J, Pasieka Z, Jankiewicz-Wika J, et al. Matrix metalloproteinases, tissue inhibitors of matrix metalloproteinases and angiogenic cytokines in peripheral blood of patients with thyroid cancer [J]. Thyroid, 2002; 12(8)∶655.
13. 　Lin SY, Wang YY, Sheu WH. Preoperative plasma concentrations of vascular endothelial growth factor and matrix metalloproteinase 9 are associated with stage progression in papillary thyroid cancer [J]. Clin Endocrinol (Oxf), 2003; 58(4)∶513.
14. 　Jumper C, Cobos E, Lox C. Determination of the serum matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) in patients with either advanced small-cell lung cancer or non-small-cell lung cancer prior to treatment [J]　. Respir Med, 2004; 98(2)∶173.
15. 　Oberg A, Hoyhtya M, Tavelin B, et al. Limited value of preoperative serum analyses of matrix metalloproteinases (MMP-2,MMP-9) and tissue inhibitors of matrix metalloproteinases (TIMP-1, TIMP-2) in colorectal cancer [J]　. Anticancer Res, 2000; 20(2B)∶1085.
16. 　Pasieka Z, Stepien H, Czyz W, et al. Concentration of metalloproteinase-2 and tissue inhibitor of metalloproteinase-2 in the serum of patients with benign and malignant thyroid tumours treated surgically [J]　. Endocr Regul, 2004; 38(2)∶57.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

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

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