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Frontiers of Medicine

ISSN 2095-0217

ISSN 2095-0225(Online)

CN 11-5983/R

Postal Subscription Code 80-967

2018 Impact Factor: 1.847

Front Med Chin    2009, Vol. 3 Issue (2) : 164-170     DOI: 10.1007/s11684-009-0038-1
RESEARCH ARTICLE |
Lymphatic metastasis is related to the epithelial-mesenchymal transition and expressions of VEGF, MMP-9, and COX-2 in breast cancer
Lihui WANG1, Lianhong LI1(), Shen LV2, Shujun FAN1, Li ZHAN3, Bo WANG1, Zhong ZHANG1
1. Department of Pathology, Dalian Medical University, Dalian 116044, China; 2. Center Laboratory, The Second Affiliated Hospital of Dalian Medical University, Dalian 116027, China; 3. Department of Pathology, Dalian Maternity Hospital, Dalian 116012, China
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Abstract  

The invasion and metastasis of breast cancer are supposed to involve several stages in which epithelial-mesenchymal transition (EMT) is regarded as the mechanistic basis for the behavior of cancer cells. A series of factors related to EMT are apparently involved in such process. The current study aimed to investigate the contributions of EMT and related factors in lymph node metastasis of breast cancer. The expressions of E-cadherin (E-Cad), N-cadherin (N-Cad), vascular endothelial cell growth factor (VEGF), matrix metalloproteinase-9 (MMP-9), cyclooxygenase-2 (COX-2), and CD34 were examined in 74 cases of breast cancer, including 39 cases with lymph node metastasis and 35 cases without lymph node metastasis by immunohistochemistry. Multivariable Cox proportional hazards model was used to analyze the patients’ prognosis. The expressions of N-Cad, VEGF, MMP-9, and COX-2 in cases with lymph node metastasis were significantly higher than those without lymph node metastasis (P<0.05), while the E-Cad level was inversely related to status of lymph node metastasis (P<0.05). The metastasis rate of lymph node in the cases with EMT (lower E-Cad expression and higher N-Cad expression) was 78.3%, while that without EMT (higher E-Cad expression and lower N-Cad expression) was 11.1%. There was a statistical difference in the expression of COX-2 protein between histological grade I and grade II or III, respectively (P<0.05). In the cases with higher grade, the expression of E-Cad was decreased, while that of N-Cad was increased. Higher microvascular density (MVD) was also found to be significantly associated with lymphatic metastasis (P<0.05), and the cases with higher MVD had shorter survival time. This study indicates that EMT and expressions of VEGF, MMP-9 and COX-2, and MVD value are strongly correlated with lymph node metastasis in breast cancer.

Keywords epithelial-mesenchymal transition      vascular endothelial cell growth factor      matrix metalloproteinase-9      cyclooxygenase-2      higher microvascular density      breast cancer     
Corresponding Authors: LI Lianhong,Email:lilianhong@dlmedu.edu.cn   
Issue Date: 05 June 2009
URL:  
http://academic.hep.com.cn/fmd/EN/10.1007/s11684-009-0038-1     OR     http://academic.hep.com.cn/fmd/EN/Y2009/V3/I2/164
proteinlymph node metastasisnexpression levelsmeanrank
-++++++
E-Cad+3981317129.68*
-352519946.21
N-Cad+390921942.38*
-3541117332.06
MMP-9+395824244.58*
-3515910129.61
VEGF+397123843.37*
-3511715230.96
COX-2+3931417542.90*
-3571710131.49
Tab.1  Relationship between the expressions of E-Cad, N-Cad, MMP-9, VEGF, COX-2, and lymph node metastasis in breast cancer
histologicalgradenE-CadN-CadCOX-2
-++++++mean rank-++++++meanrank-++++++meanrank
I190015451.340109028.50685027.16
II4491514631.52*4627739.91*41818440.14*
III11136143.41132543.41054244.82*
Tab.2  Relationship between the expressions of E-Cad, N-Cad, COX-2, and histological grade in breast cancer
nMVD
lymph node metastasis+3965.23±20.23*
-3534.60±12.96
COX-2high3361.19±24.75*
low4143.00±18.26
MMP-9high3761.43±22.46*
low3740.05±18.22
VEGFhigh4857.48±22.83*
low2638.31±17.75
Tab.3  Relationship between the expressions of COX-2, MMP-9, VEGF, and MVD value in breast cancer
Fig.1  Immunohistochemical stainings of (a) E-cadherin, (b) N-cadherin, (c) vascular endothelial cell growth factor, (d) matrix metalloproteinase-9, and (e) cyclooxygenase-2 in infiltrative ductal carcinoma, positive staining in plasma of cancer cells; (f) CD34 staining showing the microvessels (×200)
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