Correlation Between Expressions of MMP-3 and VEGF in Three Negative Breast Cancer Tissue and Their Clinical Significance_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

 GUANXiao-qing ,  ZHENGXiang-xin , WUJi , GUShu-cheng , YUANMu , ZHANGXu-xu , QIUXing , LUBo-lin

Department of General Surgery, Affiliated Suqian Hospital of Xuzhou Medical College/Suqian People's Hospital of Nanjing Drum-tower Hospital Group, Suqian 223800, Jiangsu Province, China;

Corresponding author：

ZHENGXiang-xin, Email: zhengxingxin_dr@163.com

Keywords：

Three negative breast cancer; Matrix metalloproteinase-3; Vascular endothelial growth factor; Correlation; Prognosis

DOI：

10.7507/1007-9424.20140137

Video：

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Objective To investigate the correlation between the expressions of matrix metalloproteinase-3 (MMP-3) and vascular endothelial growth factor (VEGF) in the three negative breast cancer (TNBC) and analyze their clinicopathologic significances. Methods One hundred and twelve patients confirmed TNBC from January 2008 to January 2013 in this hospital were collected. The cases of luminal type with the similar pathological type and pathological staging were chosen as control. The expressions of MMP-3 and VEGF were detected by immunohistochemistry. Results ①The positive expression rates of MMP-3 and VEGF in the TNBC tissues were significantly higher than those in the luminal tissues[MMP-3:90.18%(101/112) versus 49.11%(55/112), P < 0.05;VEGF:84.82%(95/112) versus 48.21%(54/112), P < 0.05]. 2 The positive expressions of MMP-3 and VEGF in the TNBC tissues were correlated with age, menopausal status, tumor size, axillary lymph node metastasis, and TNM stage(P < 0.05).③The expression of MMP-3 was positively correlated with VEGF in the TNBC tissues(r_s=0.711, P < 0.01).④The results of follow-up showed that the recurrence and metastasis rate within 3 years was 73.21%, the survival rate within 5 years was 36.61% in the patients with TNBC. Conclusions There is a close relation between MMP-3 and VEGF in TNBC, the expressions of MMP-3 and VEGF may serve as important biomarkers for evaluating invasion and metastasis in TNBC. There is a higher metastasis rate within 3 years and a lower survival rate within 5 years in TNBC. According to intervening the expressions of MMP-3 and VEGF, and inhibiting cancer cells matrix degradation and vascular formation, then cancer cells metastasis could be blocked, it may be important to reduce the 3-year recurrence rate and improve 5-year survival rate.

Citation： GUANXiao-qing, ZHENGXiang-xin, WUJi, GUShu-cheng, YUANMu, ZHANGXu-xu, QIUXing, LUBo-lin. Correlation Between Expressions of MMP-3 and VEGF in Three Negative Breast Cancer Tissue and Their Clinical Significance. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2014, 21(5): 567-571. doi: 10.7507/1007-9424.20140137 Copy

1.	Sørlie T, Perou CM, Tibshirani R, et al.Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications[J].Proc Natl Acad Sci USA, 2001, 98(19):10869-10874.
2.	Aksoy S, Dizdar O, Harputluoglu H, et al.Demographic, clinical, and pathological characteristics of Turkish triple-negative breast cancer patients:single center experience[J].Ann Oncol, 2007, 18(11):1904-1906.
3.	顾军, 于泽平, 李宁.三阴性乳腺癌的研究进展[J].医学研究生学报, 2010, 23(1):105-109.
4.	Baker EA, Stephenson TJ, Reed MW, et al.Expression of proteinases and inhibitors in human breast cancer progression and survival[J].Mol Pathol, 2002, 55(5):300-304.
5.	Sauter ER, Nesbit M, Watson JC, et al.Vascular endothelial growth factor is a marker of tumor invasion and metastasis in squamous cell carcinomas of the head and neck[J].Clin Cancer Res, 1999, 5(4):775-782.
6.	Adams J, Carder PJ, Downey S, et al.Vascular endothelial growth factor (VEGF) in breast cancer:comparison of plasma, serum, and tissue VEGF and microvessel density and effects of tamoxifen[J].Cancer Res, 2000, 60(11):2898-2905.
7.	Shimizu M, Saitoh Y, Itoh H.Immunohistochemical staining of Ha-ras oncogene product in normal, benign, and malignant human pancreatic tissues[J].Cancer Res, 1990, 21(6):607-612.
8.	蔡铭泉, 陈强, 施纯枚.受体三阴性乳腺癌的研究进展[J].临床肿瘤学杂志, 2009, 14(3):283-287.
9.	马睿锐, 陈琳, 陈欣, 等.183例三阴性乳腺癌临床病理特征及生存分析[J].中华普通外科杂志, 2012, 27(3):230-233.
10.	马婕, 张丽杰.受体三阴性乳腺癌的分子病理学特征和治疗研究进展[J].实用癌症杂志, 2011, 26(5):327-329.
11.	范原铭, 顾玲.三阴性乳腺癌研究进展[J].重庆医学, 2011, 40(20):2070-2073.
12.	Nielsen TO, Hsu FD, Jensen K, et al.Immunohistochemical and clinical characterization of the basal-like subtype of invasive breast carcinoma[J].Clin Cancer Res, 2004, 10(16):5367-5374.
13.	韩晓蓉, 郜红艺, 王颀, 等.三阴性乳腺癌的临床病理特点(附35例报告)[J/CD].中华乳腺病杂志:电子版, 2009, 3(1):16-21.
14.	刘杏娥, 毛伟敏.三阴性乳腺癌的生物学特征及治疗[J].肿瘤学杂志, 2009, 15(4):352-355.
15.	王瑞才, 李湘洲, 张云香, 等.MMP-3、VEGF在三阴性乳腺癌中的表达及其临床意义[J].中国现代医学杂志, 2010, 20(6):872-875.
16.	Li J, Zhang YP, Kirsner RS.Angiogenesis in wound repair:angiogenic growth factors and the extracellular matrix[J].Microsc Res Tech, 2003, 60(1):107-114.
17.	Nathanson SD.Insights into the mechanisms of lymph node metastasis[J].Cancer, 2003, 98(2):413-423.
18.	Livasy CA, Karaca G, Nanda R, et al.Phenotypic evaluation of the basal-like subtype of invasive breast carcinoma[J].Mod Pathol, 2006, 19(2):264-271.
19.	Yuli C, Shao N, Rao R, et al.BRCA1a has antitumor activity in TN breast, ovarian and prostate cancers[J].Oncogene, 2007, 26(41):6031-6037.
20.	Folgueras AR, Pendás AM, Sánchez LM, et al.Matrix metalloproteinases in cancer:from new functions to improved inhibition strategies[J].Int J Dev Biol, 2004, 48(5/6):411-424.
21.	Toriseva MJ, Ala-Aho R, Karvinen J, et al.Collagenase-3(MMP-3) enhances remodeling of three-dimensional collagen and promotes survival of human skin fibroblasts[J].J Invest Dermatol, 2007, 127(1):49-59.
22.	Tardif G, Reboul P, Pelletier JP, et al.Ten years in the life of an enzyme:the story of the human MMP-3(collagenase-3)[J].Mod Rheumatol, 2004, 14(3):197-204.
23.	苏书娟, 邢鲁奇, 陈登庭.MMP-3在乳腺导管癌中的表达及临床意义[J].现代肿瘤学杂志, 2011, 19(2):274-276.
24.	Dent R, Trudeau M, Pritchard KI, et al.Triple negativen breast cancer:clinical features and patterns of recurrence[J].Clin Cancer Res, 2007, 13:4429-4434.
25.	Tischkowitz M, Brunet JS, Begin LR, et al.Use of immunohistochemical markers can refine prognosis in triple negative breast cancer[J].BMC Cancer, 2007, 7:134.
26.	蔡欣, 高雪, 胡冬梅, 等.三阴性乳腺癌的临床特点和生存分析[J].临床肿瘤学杂志, 2010, 15(1):52-54.
27.	Hsu CP, Shen GH, Ko JL.Matrix metalloproteinase-13 expression is associated with bone marrow microinvolvement and prognosis in non-small cell lung cancer[J].Lung Cancer, 2006, 52(3):349-357.
28.	Freedman GM, Anderson PR, Li T, et al.Locoregional recurrence of triple-negative breast cancer after breast-conserving surgery and radiation[J].Cancer, 2009, 115(5):946-951.
29.	Tan AR, Swain SM.Therapeutic strategies for triple-negative breast cancer[J].Cancer J, 2008, 14(6):343-351.

1. Sørlie T, Perou CM, Tibshirani R, et al.Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications[J].Proc Natl Acad Sci USA, 2001, 98(19):10869-10874.
2. Aksoy S, Dizdar O, Harputluoglu H, et al.Demographic, clinical, and pathological characteristics of Turkish triple-negative breast cancer patients:single center experience[J].Ann Oncol, 2007, 18(11):1904-1906.
3. 顾军, 于泽平, 李宁.三阴性乳腺癌的研究进展[J].医学研究生学报, 2010, 23(1):105-109.
4. Baker EA, Stephenson TJ, Reed MW, et al.Expression of proteinases and inhibitors in human breast cancer progression and survival[J].Mol Pathol, 2002, 55(5):300-304.
5. Sauter ER, Nesbit M, Watson JC, et al.Vascular endothelial growth factor is a marker of tumor invasion and metastasis in squamous cell carcinomas of the head and neck[J].Clin Cancer Res, 1999, 5(4):775-782.
6. Adams J, Carder PJ, Downey S, et al.Vascular endothelial growth factor (VEGF) in breast cancer:comparison of plasma, serum, and tissue VEGF and microvessel density and effects of tamoxifen[J].Cancer Res, 2000, 60(11):2898-2905.
7. Shimizu M, Saitoh Y, Itoh H.Immunohistochemical staining of Ha-ras oncogene product in normal, benign, and malignant human pancreatic tissues[J].Cancer Res, 1990, 21(6):607-612.
8. 蔡铭泉, 陈强, 施纯枚.受体三阴性乳腺癌的研究进展[J].临床肿瘤学杂志, 2009, 14(3):283-287.
9. 马睿锐, 陈琳, 陈欣, 等.183例三阴性乳腺癌临床病理特征及生存分析[J].中华普通外科杂志, 2012, 27(3):230-233.
10. 马婕, 张丽杰.受体三阴性乳腺癌的分子病理学特征和治疗研究进展[J].实用癌症杂志, 2011, 26(5):327-329.
11. 范原铭, 顾玲.三阴性乳腺癌研究进展[J].重庆医学, 2011, 40(20):2070-2073.
12. Nielsen TO, Hsu FD, Jensen K, et al.Immunohistochemical and clinical characterization of the basal-like subtype of invasive breast carcinoma[J].Clin Cancer Res, 2004, 10(16):5367-5374.
13. 韩晓蓉, 郜红艺, 王颀, 等.三阴性乳腺癌的临床病理特点(附35例报告)[J/CD].中华乳腺病杂志:电子版, 2009, 3(1):16-21.
14. 刘杏娥, 毛伟敏.三阴性乳腺癌的生物学特征及治疗[J].肿瘤学杂志, 2009, 15(4):352-355.
15. 王瑞才, 李湘洲, 张云香, 等.MMP-3、VEGF在三阴性乳腺癌中的表达及其临床意义[J].中国现代医学杂志, 2010, 20(6):872-875.
16. Li J, Zhang YP, Kirsner RS.Angiogenesis in wound repair:angiogenic growth factors and the extracellular matrix[J].Microsc Res Tech, 2003, 60(1):107-114.
17. Nathanson SD.Insights into the mechanisms of lymph node metastasis[J].Cancer, 2003, 98(2):413-423.
18. Livasy CA, Karaca G, Nanda R, et al.Phenotypic evaluation of the basal-like subtype of invasive breast carcinoma[J].Mod Pathol, 2006, 19(2):264-271.
19. Yuli C, Shao N, Rao R, et al.BRCA1a has antitumor activity in TN breast, ovarian and prostate cancers[J].Oncogene, 2007, 26(41):6031-6037.
20. Folgueras AR, Pendás AM, Sánchez LM, et al.Matrix metalloproteinases in cancer:from new functions to improved inhibition strategies[J].Int J Dev Biol, 2004, 48(5/6):411-424.
21. Toriseva MJ, Ala-Aho R, Karvinen J, et al.Collagenase-3(MMP-3) enhances remodeling of three-dimensional collagen and promotes survival of human skin fibroblasts[J].J Invest Dermatol, 2007, 127(1):49-59.
22. Tardif G, Reboul P, Pelletier JP, et al.Ten years in the life of an enzyme:the story of the human MMP-3(collagenase-3)[J].Mod Rheumatol, 2004, 14(3):197-204.
23. 苏书娟, 邢鲁奇, 陈登庭.MMP-3在乳腺导管癌中的表达及临床意义[J].现代肿瘤学杂志, 2011, 19(2):274-276.
24. Dent R, Trudeau M, Pritchard KI, et al.Triple negativen breast cancer:clinical features and patterns of recurrence[J].Clin Cancer Res, 2007, 13:4429-4434.
25. Tischkowitz M, Brunet JS, Begin LR, et al.Use of immunohistochemical markers can refine prognosis in triple negative breast cancer[J].BMC Cancer, 2007, 7:134.
26. 蔡欣, 高雪, 胡冬梅, 等.三阴性乳腺癌的临床特点和生存分析[J].临床肿瘤学杂志, 2010, 15(1):52-54.
27. Hsu CP, Shen GH, Ko JL.Matrix metalloproteinase-13 expression is associated with bone marrow microinvolvement and prognosis in non-small cell lung cancer[J].Lung Cancer, 2006, 52(3):349-357.
28. Freedman GM, Anderson PR, Li T, et al.Locoregional recurrence of triple-negative breast cancer after breast-conserving surgery and radiation[J].Cancer, 2009, 115(5):946-951.
29. Tan AR, Swain SM.Therapeutic strategies for triple-negative breast cancer[J].Cancer J, 2008, 14(6):343-351.

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Correlation Between Expressions of MMP-3 and VEGF in Three Negative Breast Cancer Tissue and Their Clinical Significance

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