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.	王東升, 錢向龍, 張浩. 對cN0甲狀腺乳頭狀癌行中央區淋巴結清掃的臨床意義 [Ｊ]. 山東醫藥, 2007; 47(21): 79-80.
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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.	王偉，尹家俊，路小光, 等. MMP-2和CD44v6蛋白表達與胃癌生物學行為相關性的實驗研究 [Ｊ]. 中國腫瘤臨床與康復, 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.	姚曉峰, 張侖, 鄭紅, 等. MMP-2 和TIMP-2 在甲狀腺癌中的表達及其意義 [Ｊ]. 天津醫科大學學報， 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, 魏啟幼, 范松青. 甲狀腺乳頭狀癌中VEGF-C、TAMs 的表達及意義 [Ｊ]. 診斷病理學雜志, 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.	劉經祖. 分化型甲狀腺癌外科手術方式 [Ｊ]. 中國實用外科雜志, 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.	盧增紅，楊安奎，宋明, 等. cN0期甲狀腺乳頭狀癌Ⅵ區淋巴結處理探討78例報告 [Ｊ]. 中國腫瘤, 2006; 15(1): 58-60.
25.	佟麗波, 藤靜, 佟秀鳳. MMP-2、VEGF-C、CD44V6在宮頸癌中的表達及其與侵襲、轉移的關系 [Ｊ]. 黑龍江醫藥科學, 2007; 30(4): 10-11.

1. 王東升, 錢向龍, 張浩. 對cN0甲狀腺乳頭狀癌行中央區淋巴結清掃的臨床意義 [Ｊ]. 山東醫藥, 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. 王偉，尹家俊，路小光, 等. MMP-2和CD44v6蛋白表達與胃癌生物學行為相關性的實驗研究 [Ｊ]. 中國腫瘤臨床與康復, 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. 姚曉峰, 張侖, 鄭紅, 等. MMP-2 和TIMP-2 在甲狀腺癌中的表達及其意義 [Ｊ]. 天津醫科大學學報， 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, 魏啟幼, 范松青. 甲狀腺乳頭狀癌中VEGF-C、TAMs 的表達及意義 [Ｊ]. 診斷病理學雜志, 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. 劉經祖. 分化型甲狀腺癌外科手術方式 [Ｊ]. 中國實用外科雜志, 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. 盧增紅，楊安奎，宋明, 等. cN0期甲狀腺乳頭狀癌Ⅵ區淋巴結處理探討78例報告 [Ｊ]. 中國腫瘤, 2006; 15(1): 58-60.
25. 佟麗波, 藤靜, 佟秀鳳. MMP-2、VEGF-C、CD44V6在宮頸癌中的表達及其與侵襲、轉移的關系 [Ｊ]. 黑龍江醫藥科學, 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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