Relation Between Epithelial Mesenchymal Transition Related Proteins Expressions and Clinicopathologic Features or Prognosis of Patients with Invasive Ductal Carcinoma of Breast_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

 QIANJin-feng ¹ ,  YANGQi-chang ¹ , XIEHui-jun ² , LIUHong-bin ¹ , ZHANGXiao-juan ¹ , ZHUYan ¹

1. Department of Pathology, The Second Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China;
2. Department of Pathology, Nantong Rich Hospital of Jiangsu Province, Nantong 226010, Jiangsu Province, China;

Corresponding author：

YANGQi-chang, Email: ntyangqc@163.com

Keywords：

Breast invasive ductal carcinoma; Epithelial mesenchymal transition; Clinicopathologic factor

DOI：

10.7507/1007-9424.20150155

Video：

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Objective To investigate the relationship of epithelial mesenchymal transition (EMT) related proteins expressions in invasive ductal carcinoma of breast to its clinicopathologic features and prognosis. Methods The expressions of EMT related proteins (Vimentin, E-cadherin, and MMP2) in the 118 cases of invasive ductal carcinoma of breast and 30 cases of corresponding normal breast tissues adjacent to cancer were detected by immunohistochemistry. The relationship of EMT related proteins expressions to age, tumor site, tumor size, lymph node metastasis, histological grade, TNM stage or prognosis of the patients with invasive ductal carcinoma of breast was analyzed. Results ①The positive rates of the Vimentin protein and MMP2 protein in the invasive ductal carcinoma of breast were significantly higher than those in the corresponding normal breast tissues adjacent to cancer﹝Vimentin protein: 50.8% (60/118) versus 10.0% (3/30), P < 0.05; MMP2 protein: 63.6% (75/118) versus 6.7% (2/30), P < 0.05﹞, the positive rate of E-cadherin in the invasive ductal carcinoma of breast was significantly lower than that in the corresponding normal breast tissues adjacent to cancer ﹝56.8% (67/118) versus 93.3% (28/30), P < 0.05﹞.②The positive rate of the Vimentin protein expression in the invasive ductal carcinoma tissue was positively related with the lymph node metastasis and TNM staging (r_s=0.346, P < 0.05; r_s=0.231, P < 0.05). The positive rate of the E-cadherin or MMP2 protein expression was negatively or positively related with the tumor size, lymph node metastasis, histological grade, and TNM stage (E-cadherin: r_s=-0.444, P < 0.05; r_s=-0.493, P < 0.05; r_s=-0.323, P < 0.05; r_s=-0.474, P < 0.05. MMP2: r_s=0.361, P < 0.05; r_s=0.434, P < 0.05; r_s=0.396, P < 0.05; r_s=0.376, P < 0.05).③The Kaplan-Meier survival curve analysis showed that the positive expressions of Vimentin and MMP2 were stronger, the tumor free survival time was shorter (P < 0.05), and the positive expression of E-cadherin was stronger, the tumor free survival time was longer (P < 0.05). Conclusion Joint detection of EMT related proteins (Vimentin, E-cadherin, MMP2) of invasive ductal carcinoma tissue of breast could predict the pathological grade and clinical stage, as well as effective prognosis of patients with invasive ductal carcinoma of breast in clinical.

Citation： QIANJin-feng, YANGQi-chang, XIEHui-jun, LIUHong-bin, ZHANGXiao-juan, ZHUYan. Relation Between Epithelial Mesenchymal Transition Related Proteins Expressions and Clinicopathologic Features or Prognosis of Patients with Invasive Ductal Carcinoma of Breast. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2015, 22(5): 591-596. doi: 10.7507/1007-9424.20150155 Copy

1.	郑莹, 吴春晓, 张敏璐.乳腺癌在中国的流行状况和疾病特征.中国癌症杂志, 2013, 23(8):561-569.
2.	Thiery JP, Acloque H, Huang RY, et al. Epithelial-mesenchymal transitions in development and disease. Cell, 2009, 139(5):871-890.
3.	Boyer B, Vallés AM, Edme N. Induction and regulation of epithelial-mesenchymal transitions. Biochem Pharmacol, 2000, 60(8):1091-1099.
4.	徐江锋, 罗庚求.上皮细胞间质转型与肿瘤转移.国际病理科学与临床杂志, 2007, 27(5):393-396.
5.	Rhodes A, Jasani B, Balaton AJ, et al. Study of interlaboratory reliability and reproducibility of estrogen and progesterone receptor assays in Europe. Documentation of poor reliability and identification of insufficient microwave antigen retrieval time as a major contributory element of unreliable assays. Am J Clin Pathol, 2001, 115(1):44-58.
6.	Baumgart E, Cohen MS, Neto BS, et al. Identification and prognostic significance of an epithelial-mesenchymal transition expression profile in human bladder tumors. Clin Cancer Res, 2007, 13(6):1685-1694.
7.	Esposito NN, Chivukula M, Dabbs DJ. The ductal phenotypic expression of the E-cadherin/catenin complex in tubulolobular carcinoma of the breast:an immunohistochemical and clinicopathologic study. Mod Pathol, 2007, 20(1):130-138.
8.	Bindels S, Mestdagt M, Vandewalle C, et al. Regulation of vimentin by SIP1 in human epithelial breast tumor cells. Oncogene, 2006, 25(36):4975-4985.
9.	Graham TR, Zhau HE, Odero-Marah VA, et al. Insulin-like growth factor-Ⅰ-dependent up-regulation of ZEB1 drives epithelial-to-mesenchymal transition in human prostate cancer cells. Cancer Res, 2008, 68(7):2479-2488.
10.	Saitoh M, Miyazawa K. Transcriptional and post-transcriptional regulation in TGF-beta-mediated epithelial-mesenchymal transition. J Biochem, 2012, 151(6):563-571.
11.	Heldin CH, Vanlandewijck M, Moustakas A. Regulation of EMT by TGFβin cancer. FEBS Lett, 2012, 586(14):1959-1970.
12.	蔡成, 俞继卫, 吴巨钢, 等.胃癌原发灶中上皮间质转化相关因子和CD133的表达及其与临床病理特征和预后的关系.中国普外基础与临床杂志, 2013, 5(5):492-498.
13.	Miladi-Abdennadher I, Abdelmaksoud-Dammak R, Ayed-Guerfali DB, et al. Expression of COX-2 and E-cadherin in Tunisian patients with colorectal adenocarcinoma. Acta Histochem, 2012, 114(6):577-581.
14.	苏云涛, 许妍洁, 仇金荣, 等.上皮间质转化分子标记物在乳腺浸润性导管癌组织中的表达及临床意义.临床肿瘤学杂志, 2012, 17(6):505-510.
15.	Bhuvarahamurthy V, Kristiansen GO, Johannsen M, et al. In situ gene expression and localization of metalloproteinases MMP1, MMP2, MMP3, MMP9, and their inhibitors TIMP1 and TIMP2 in human renal cell carcinoma. Oncol Rep, 2006, 15(5):1379-1384.
16.	Temma T, Sano K, Kuge Y, et al. Development of a radiolabeled probe for detecting membrane type-1 matrix metalloproteinase on malignant tumors. Biol Pharm Bull, 2009, 32(7):1272-1277.
17.	Giannopoulos G, Pavlakis K, Parasi AA, et al. The expression of matrix metalloproteinases-2 and-9 and their tissue inhibitor 2 in pancreatic ductal and ampullary carcinoma and their relation to angiogenesis and clinicopathological parameters. Anticancer Res, 2008, 28(3B):1875-1881.
18.	Overall CM, Dean RA. Degradomics:systems biology of the protease web. Pleiotropic roles of MMPs in cancer. Cancer Metastasis Rev, 2006, 25(1):69-75.
19.	Olszyński K, Zimowska M. Structure and function of matrix metalloproteinases. Postepy Biochem, 2009, 55(1):76-84.
20.	Sun J, Hemler ME. Regulation of MMP-1 and MMP-2 production through CD147/extracellular matrix metalloproteinase inducer interactions. Cancer Res, 2001, 61(5):2276-2281.
21.	Shah FD, Shukla SN, Shah PM, et al. Clinical significance of matrix metalloproteinase 2 and 9 in breast cancer. Indian J Cancer, 2009, 46(3):194-202.
22.	Li HC, Cao DC, Liu Y, et al. Prognostic value of matrix metalloproteinases (MMP-2 and MMP-9) in patients with lymph node-negative breast carcinoma. Breast Cancer Res Treat, 2004, 88(1):75-85.
23.	苏书娟, 邢鲁奇, 陈登庭, 等. MMP-2、MMP-9在乳腺导管癌中表达及意义.中国公共卫生, 2011, 27(3):268-270.
24.	朱之坤, 刘志容, 吴诚义. MMP-3与乳腺癌上皮间质转化的关系及其意义.生命科学研究, 2012, 16(1):63-67.
25.	刘志容, 吴诚义. MMP-3、Vimentin联合检测与乳腺癌侵袭转移的关系.肿瘤防治研究, 2012, 39(2):222-224.
26.	王凤琴. Twist、E-cadherin蛋白在乳腺良恶性病变中的表达与EMT的关系及其意义.医学临床研究, 2011, 28(10):1864-1867.
27.	祝立和, 卢洪胜, 周凯敏, 等. STAT3蛋白激活与乳腺浸润性导管癌上皮间质转化的相关性研究.中国现代医生, 2012, 50(17):106-109, 161.

1. 郑莹, 吴春晓, 张敏璐.乳腺癌在中国的流行状况和疾病特征.中国癌症杂志, 2013, 23(8):561-569.
2. Thiery JP, Acloque H, Huang RY, et al. Epithelial-mesenchymal transitions in development and disease. Cell, 2009, 139(5):871-890.
3. Boyer B, Vallés AM, Edme N. Induction and regulation of epithelial-mesenchymal transitions. Biochem Pharmacol, 2000, 60(8):1091-1099.
4. 徐江锋, 罗庚求.上皮细胞间质转型与肿瘤转移.国际病理科学与临床杂志, 2007, 27(5):393-396.
5. Rhodes A, Jasani B, Balaton AJ, et al. Study of interlaboratory reliability and reproducibility of estrogen and progesterone receptor assays in Europe. Documentation of poor reliability and identification of insufficient microwave antigen retrieval time as a major contributory element of unreliable assays. Am J Clin Pathol, 2001, 115(1):44-58.
6. Baumgart E, Cohen MS, Neto BS, et al. Identification and prognostic significance of an epithelial-mesenchymal transition expression profile in human bladder tumors. Clin Cancer Res, 2007, 13(6):1685-1694.
7. Esposito NN, Chivukula M, Dabbs DJ. The ductal phenotypic expression of the E-cadherin/catenin complex in tubulolobular carcinoma of the breast:an immunohistochemical and clinicopathologic study. Mod Pathol, 2007, 20(1):130-138.
8. Bindels S, Mestdagt M, Vandewalle C, et al. Regulation of vimentin by SIP1 in human epithelial breast tumor cells. Oncogene, 2006, 25(36):4975-4985.
9. Graham TR, Zhau HE, Odero-Marah VA, et al. Insulin-like growth factor-Ⅰ-dependent up-regulation of ZEB1 drives epithelial-to-mesenchymal transition in human prostate cancer cells. Cancer Res, 2008, 68(7):2479-2488.
10. Saitoh M, Miyazawa K. Transcriptional and post-transcriptional regulation in TGF-beta-mediated epithelial-mesenchymal transition. J Biochem, 2012, 151(6):563-571.
11. Heldin CH, Vanlandewijck M, Moustakas A. Regulation of EMT by TGFβin cancer. FEBS Lett, 2012, 586(14):1959-1970.
12. 蔡成, 俞继卫, 吴巨钢, 等.胃癌原发灶中上皮间质转化相关因子和CD133的表达及其与临床病理特征和预后的关系.中国普外基础与临床杂志, 2013, 5(5):492-498.
13. Miladi-Abdennadher I, Abdelmaksoud-Dammak R, Ayed-Guerfali DB, et al. Expression of COX-2 and E-cadherin in Tunisian patients with colorectal adenocarcinoma. Acta Histochem, 2012, 114(6):577-581.
14. 苏云涛, 许妍洁, 仇金荣, 等.上皮间质转化分子标记物在乳腺浸润性导管癌组织中的表达及临床意义.临床肿瘤学杂志, 2012, 17(6):505-510.
15. Bhuvarahamurthy V, Kristiansen GO, Johannsen M, et al. In situ gene expression and localization of metalloproteinases MMP1, MMP2, MMP3, MMP9, and their inhibitors TIMP1 and TIMP2 in human renal cell carcinoma. Oncol Rep, 2006, 15(5):1379-1384.
16. Temma T, Sano K, Kuge Y, et al. Development of a radiolabeled probe for detecting membrane type-1 matrix metalloproteinase on malignant tumors. Biol Pharm Bull, 2009, 32(7):1272-1277.
17. Giannopoulos G, Pavlakis K, Parasi AA, et al. The expression of matrix metalloproteinases-2 and-9 and their tissue inhibitor 2 in pancreatic ductal and ampullary carcinoma and their relation to angiogenesis and clinicopathological parameters. Anticancer Res, 2008, 28(3B):1875-1881.
18. Overall CM, Dean RA. Degradomics:systems biology of the protease web. Pleiotropic roles of MMPs in cancer. Cancer Metastasis Rev, 2006, 25(1):69-75.
19. Olszyński K, Zimowska M. Structure and function of matrix metalloproteinases. Postepy Biochem, 2009, 55(1):76-84.
20. Sun J, Hemler ME. Regulation of MMP-1 and MMP-2 production through CD147/extracellular matrix metalloproteinase inducer interactions. Cancer Res, 2001, 61(5):2276-2281.
21. Shah FD, Shukla SN, Shah PM, et al. Clinical significance of matrix metalloproteinase 2 and 9 in breast cancer. Indian J Cancer, 2009, 46(3):194-202.
22. Li HC, Cao DC, Liu Y, et al. Prognostic value of matrix metalloproteinases (MMP-2 and MMP-9) in patients with lymph node-negative breast carcinoma. Breast Cancer Res Treat, 2004, 88(1):75-85.
23. 苏书娟, 邢鲁奇, 陈登庭, 等. MMP-2、MMP-9在乳腺导管癌中表达及意义.中国公共卫生, 2011, 27(3):268-270.
24. 朱之坤, 刘志容, 吴诚义. MMP-3与乳腺癌上皮间质转化的关系及其意义.生命科学研究, 2012, 16(1):63-67.
25. 刘志容, 吴诚义. MMP-3、Vimentin联合检测与乳腺癌侵袭转移的关系.肿瘤防治研究, 2012, 39(2):222-224.
26. 王凤琴. Twist、E-cadherin蛋白在乳腺良恶性病变中的表达与EMT的关系及其意义.医学临床研究, 2011, 28(10):1864-1867.
27. 祝立和, 卢洪胜, 周凯敏, 等. STAT3蛋白激活与乳腺浸润性导管癌上皮间质转化的相关性研究.中国现代医生, 2012, 50(17):106-109, 161.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Relation Between Epithelial Mesenchymal Transition Related Proteins Expressions and Clinicopathologic Features or Prognosis of Patients with Invasive Ductal Carcinoma of Breast

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