Expressions and Clinical Significance of MMP-2 and VEGF-C in Papillary Thyroid Carcinoma_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

WU Ligang , LIU Qilun , HU Zhiqiang

Department of Surgical Oncology, Affiliated Hospital of Ningxia Medical University, Yinchuan 750004, China;

Corresponding author：

Keywords：

Papillary thyroid carcinoma; Immunohistochemistry; Matrix metalloproteinases-2; Vascular endothelial growth factor-C

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Objective To study the expressions and clinical significance of matrix metalloproteinases-2 (MMP-2) and vascular endothelial growth factor-C (VEGF-C) in patients with papillary thyroid carcinoma (PTC). Methods SP immunohistochemical technique was used to detect the expressions of MMP-2 and VEGF-C in 78 cases of PTC and 18 cases of thyroid benign tumors.Results The positive expression rates of MMP-2 and VEGF-C in PTC （80.77%, 75.64%） were significantly higher than those of the thyroid benign tumor （11.11%, 22.22%）, P＜0.05. The expressions of MMP-2 and VEGF-C were correlated to the degree of infiltration and lymph node metastasis in PTC: In those which infiltrated to or over the thyroid capsular, or had clinical neck lymph node metastasis, the positive expression rates were significantly higher than those in the other cases which had confined invasion of thyroid capsular or non-clinical metastasis of neck lymph node (P＜0.05). And during the follow-up of 41 patients who didn’t have clinical neck lymph node metastasis before operation, the positive expression rates of those who had clinical neck lymph node metastasis were significantly higher than those in the other patients who didn’t have neck lymph node metastasis (P＜0.05). There was significantly positive correlation between the expressions of MMP-2 and VEGF-C in PTC （Gamma=0.846， P＜0.05）. Conclusions MMP-2 and VEGF-C may be used to distinguish malignant and benign thyroid tumor; The expressions of MMP-2 and VEGF-C are correlated with the degree of infiltration and neck lymph node metastasis in PTC; Combined detection of MMP-2 and VEGF-C will be more accurate to predict condition of lymph node metastasis.

Citation： WU Ligang,LIU Qilun,HU Zhiqiang. Expressions and Clinical Significance of MMP-2 and VEGF-C in Papillary Thyroid Carcinoma. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2009, 16(11): 906-910. doi: Copy

1.	王东升, 钱向龙, 张浩. 对cN0甲状腺乳头状癌行中央区淋巴结清扫的临床意义 [Ｊ]. 山东医药, 2007; 47(21): 79-80.
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3.	Neuchrist C, Erovic BM, Handisurya A, et al. Vascular endothelial growth factor C and vascular endothelial growth factor receptor 3 expression in squamous cell carcinomas of the head and neck [Ｊ]. Head Neck, 2003; 25(6): 464-474.
4.	Ishikawa M, Kitayama J, Kazama S, et al. Expression of vascular endothelial growth factor C and D (VEGF-C and -D) is an important risk factor for lymphatic metastasis in undifferentiated early gastric carcinoma [Ｊ]. Jpn J Clin Oncol, 2003; 33(1): 21-27.
5.	Lymboussaki A, Olofsson B, Eriksson U，et al. Vascular endothelial growth factor (VEGF) and VEGF-C show overlapping binding sites in embryonic endothelia and distinct sites in differentiated adult endothelia [Ｊ]. Circ Res, 1999; 85(11): 992-999.
6.	Itoh Y, Ito N, Nagase H, et al. Cell surface collagenolysis requires homodimerization of the membrane-bound collagenase MT1-MMP [Ｊ]. Mol Biol Cell, 2006; 17(12): 5390-5399.
7.	王伟，尹家俊，路小光, 等. MMP-2和CD44v6蛋白表达与胃癌生物学行为相关性的实验研究 [Ｊ]. 中国肿瘤临床与康复, 2005; 12(6): 502-506.
8.	Cai M, Onoda K, Takao M, et al. Degradation of tenascin-C and activity of matrix metalloproteinase-2 are associated with tumor recurrence in early stage non-small cell lung cancer [Ｊ]. Clin Cancer Res, 2002; 8(4): 1152-1156.
9.	Maruyama S, Kawata R, Shimada T, et al. Study of matrix metalloproteinase-2 and -9 in thyroid papillary cancer [Ｊ]. Nippon Jibiinkoka Gakkai Kaiho, 2000; 103(5): 499-505.
10.	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): 881-888.
11.	姚晓峰, 张仑, 郑红, 等. MMP-2 和TIMP-2 在甲状腺癌中的表达及其意义 [Ｊ]. 天津医科大学学报， 2007; 13（4）： 552-555.
12.	Shiomi T, Okada Y. MT1-MMP and MMP-7 in invasion and metastasis of human cancers [Ｊ]. Cancer Metastasis Rev, 2003; 22(2-3): 145-152.
13.	Loukopoulos P, Mungall BA, Straw RC, et al. Matrix metalloproteinase-2 and -9 involvement in canine tumors [Ｊ]. Vet Pathol, 2003; 40(4): 382-394.
14.	Abdel-Ghany M, Cheng HC, Elble RC, et al. The breast ca-ncer beta 4 integrin and endothelial human CLCA2 mediate lung metastasis [Ｊ]. J Biol Chem, 2001; 276(27): 25438-25446.
15.	Joukov V, Pajusola K, Kaipainen A, et al. A novel vascular endothelial growth factor, VEGF-C, is a ligand for the Flt4 (VEGFR-3) and KDR (VEGFR-2) receptor tyrosine kinases [Ｊ]. EMBO J, 1996; 15(2): 290-298.
16.	Fellmer PT, Sato K, Tanaka R, et al. Vascular endothelial growth factor-C gene expression in papillary and follicular thyroid carcinomas [Ｊ]. Surgery, 1999; 126(6): 1056-1061; discussion 1061-1062.
17.	Hung CJ, Ginzinger DG, Zarnegar R, et al. Expression of vascular endothelial growth factor-C in benign and malignant thyroid tumors [Ｊ]. J Clin Endocrinol Metab, 2003; 88(8): 3694-3699.
18.	梁青春, 魏启幼, 范松青. 甲状腺乳头状癌中VEGF-C、TAMs 的表达及意义 [Ｊ]. 诊断病理学杂志, 2006; 13（2）: 144-145.
19.	Stacker SA, Achen MG, Jussila L, et al. Lymphangiogenesis and cancer metastasis [Ｊ]. Nat Rev Cancer, 2002; 2(8): 573-583.
20.	Carmeliet P, Jain RK. Angiogenesis in cancer and other diseases [Ｊ]. Nature, 2000; 407(6801): 249-257.
21.	Saharinen P, Tammela T, Karkkainen MJ， et al. Lymphatic vasculature: development, molecular regulation and role in tumor metastasis and inflammation [Ｊ]. Trends Immunol, 2004; 25(7): 387-395.
22.	刘经祖. 分化型甲状腺癌外科手术方式 [Ｊ]. 中国实用外科杂志, 2004; 24(10): 579-581.
23.	Zaman K, Driscoll R, Hahn D, et al. Monitoring multiple angiogenesis-related molecules in the blood of cancer patients shows a correlation between VEGF-A and MMP-9 levels before treatment and divergent changes after surgical vs. conservative therapy [Ｊ]. Int J Cancer, 2006; 118(3): 755-764.
24.	卢增红，杨安奎，宋明, 等. cN0期甲状腺乳头状癌Ⅵ区淋巴结处理探讨78例报告 [Ｊ]. 中国肿瘤, 2006; 15(1): 58-60.
25.	佟丽波, 藤静, 佟秀凤. MMP-2、VEGF-C、CD44V6在宫颈癌中的表达及其与侵袭、转移的关系 [Ｊ]. 黑龙江医药科学, 2007; 30(4): 10-11.

1. 王东升, 钱向龙, 张浩. 对cN0甲状腺乳头状癌行中央区淋巴结清扫的临床意义 [Ｊ]. 山东医药, 2007; 47(21): 79-80.
2. Leboulleux S, Rubino C, Baudin E, et al. Prognostic factors for persistent or recurrent disease of papillary thyroid carcinoma with neck lymph node metastases and/or tumor extension beyond the thyroid capsule at initial diagnosis [Ｊ]. J Clin Endocrinol Metab, 2005; 90(10): 5723-5729.
3. Neuchrist C, Erovic BM, Handisurya A, et al. Vascular endothelial growth factor C and vascular endothelial growth factor receptor 3 expression in squamous cell carcinomas of the head and neck [Ｊ]. Head Neck, 2003; 25(6): 464-474.
4. Ishikawa M, Kitayama J, Kazama S, et al. Expression of vascular endothelial growth factor C and D (VEGF-C and -D) is an important risk factor for lymphatic metastasis in undifferentiated early gastric carcinoma [Ｊ]. Jpn J Clin Oncol, 2003; 33(1): 21-27.
5. Lymboussaki A, Olofsson B, Eriksson U，et al. Vascular endothelial growth factor (VEGF) and VEGF-C show overlapping binding sites in embryonic endothelia and distinct sites in differentiated adult endothelia [Ｊ]. Circ Res, 1999; 85(11): 992-999.
6. Itoh Y, Ito N, Nagase H, et al. Cell surface collagenolysis requires homodimerization of the membrane-bound collagenase MT1-MMP [Ｊ]. Mol Biol Cell, 2006; 17(12): 5390-5399.
7. 王伟，尹家俊，路小光, 等. MMP-2和CD44v6蛋白表达与胃癌生物学行为相关性的实验研究 [Ｊ]. 中国肿瘤临床与康复, 2005; 12(6): 502-506.
8. Cai M, Onoda K, Takao M, et al. Degradation of tenascin-C and activity of matrix metalloproteinase-2 are associated with tumor recurrence in early stage non-small cell lung cancer [Ｊ]. Clin Cancer Res, 2002; 8(4): 1152-1156.
9. Maruyama S, Kawata R, Shimada T, et al. Study of matrix metalloproteinase-2 and -9 in thyroid papillary cancer [Ｊ]. Nippon Jibiinkoka Gakkai Kaiho, 2000; 103(5): 499-505.
10. 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): 881-888.
11. 姚晓峰, 张仑, 郑红, 等. MMP-2 和TIMP-2 在甲状腺癌中的表达及其意义 [Ｊ]. 天津医科大学学报， 2007; 13（4）： 552-555.
12. Shiomi T, Okada Y. MT1-MMP and MMP-7 in invasion and metastasis of human cancers [Ｊ]. Cancer Metastasis Rev, 2003; 22(2-3): 145-152.
13. Loukopoulos P, Mungall BA, Straw RC, et al. Matrix metalloproteinase-2 and -9 involvement in canine tumors [Ｊ]. Vet Pathol, 2003; 40(4): 382-394.
14. Abdel-Ghany M, Cheng HC, Elble RC, et al. The breast ca-ncer beta 4 integrin and endothelial human CLCA2 mediate lung metastasis [Ｊ]. J Biol Chem, 2001; 276(27): 25438-25446.
15. Joukov V, Pajusola K, Kaipainen A, et al. A novel vascular endothelial growth factor, VEGF-C, is a ligand for the Flt4 (VEGFR-3) and KDR (VEGFR-2) receptor tyrosine kinases [Ｊ]. EMBO J, 1996; 15(2): 290-298.
16. Fellmer PT, Sato K, Tanaka R, et al. Vascular endothelial growth factor-C gene expression in papillary and follicular thyroid carcinomas [Ｊ]. Surgery, 1999; 126(6): 1056-1061; discussion 1061-1062.
17. Hung CJ, Ginzinger DG, Zarnegar R, et al. Expression of vascular endothelial growth factor-C in benign and malignant thyroid tumors [Ｊ]. J Clin Endocrinol Metab, 2003; 88(8): 3694-3699.
18. 梁青春, 魏启幼, 范松青. 甲状腺乳头状癌中VEGF-C、TAMs 的表达及意义 [Ｊ]. 诊断病理学杂志, 2006; 13（2）: 144-145.
19. Stacker SA, Achen MG, Jussila L, et al. Lymphangiogenesis and cancer metastasis [Ｊ]. Nat Rev Cancer, 2002; 2(8): 573-583.
20. Carmeliet P, Jain RK. Angiogenesis in cancer and other diseases [Ｊ]. Nature, 2000; 407(6801): 249-257.
21. Saharinen P, Tammela T, Karkkainen MJ， et al. Lymphatic vasculature: development, molecular regulation and role in tumor metastasis and inflammation [Ｊ]. Trends Immunol, 2004; 25(7): 387-395.
22. 刘经祖. 分化型甲状腺癌外科手术方式 [Ｊ]. 中国实用外科杂志, 2004; 24(10): 579-581.
23. Zaman K, Driscoll R, Hahn D, et al. Monitoring multiple angiogenesis-related molecules in the blood of cancer patients shows a correlation between VEGF-A and MMP-9 levels before treatment and divergent changes after surgical vs. conservative therapy [Ｊ]. Int J Cancer, 2006; 118(3): 755-764.
24. 卢增红，杨安奎，宋明, 等. cN0期甲状腺乳头状癌Ⅵ区淋巴结处理探讨78例报告 [Ｊ]. 中国肿瘤, 2006; 15(1): 58-60.
25. 佟丽波, 藤静, 佟秀凤. MMP-2、VEGF-C、CD44V6在宫颈癌中的表达及其与侵袭、转移的关系 [Ｊ]. 黑龙江医药科学, 2007; 30(4): 10-11.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Expressions and Clinical Significance of MMP-2 and VEGF-C in Papillary Thyroid Carcinoma

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