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.	鄭瑩, 吳春曉, 張敏璐.乳腺癌在中國的流行狀況和疾病特征.中國癌癥雜志, 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.	徐江鋒, 羅庚求.上皮細胞間質轉型與腫瘤轉移.國際病理科學與臨床雜志, 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, 俞繼衛, 吳巨鋼, 等.胃癌原發灶中上皮間質轉化相關因子和CD133的表達及其與臨床病理特征和預后的關系.中國普外基礎與臨床雜志, 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.	蘇云濤, 許妍潔, 仇金榮, 等.上皮間質轉化分子標記物在乳腺浸潤性導管癌組織中的表達及臨床意義.臨床腫瘤學雜志, 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.	蘇書娟, 邢魯奇, 陳登庭, 等. MMP-2、MMP-9在乳腺導管癌中表達及意義.中國公共衛生, 2011, 27(3):268-270.
24.	朱之坤, 劉志容, 吳誠義. MMP-3與乳腺癌上皮間質轉化的關系及其意義.生命科學研究, 2012, 16(1):63-67.
25.	劉志容, 吳誠義. MMP-3、Vimentin聯合檢測與乳腺癌侵襲轉移的關系.腫瘤防治研究, 2012, 39(2):222-224.
26.	王鳳琴. Twist、E-cadherin蛋白在乳腺良惡性病變中的表達與EMT的關系及其意義.醫學臨床研究, 2011, 28(10):1864-1867.
27.	祝立和, 盧洪勝, 周凱敏, 等. STAT3蛋白激活與乳腺浸潤性導管癌上皮間質轉化的相關性研究.中國現代醫生, 2012, 50(17):106-109, 161.

1. 鄭瑩, 吳春曉, 張敏璐.乳腺癌在中國的流行狀況和疾病特征.中國癌癥雜志, 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. 徐江鋒, 羅庚求.上皮細胞間質轉型與腫瘤轉移.國際病理科學與臨床雜志, 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, 俞繼衛, 吳巨鋼, 等.胃癌原發灶中上皮間質轉化相關因子和CD133的表達及其與臨床病理特征和預后的關系.中國普外基礎與臨床雜志, 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. 蘇云濤, 許妍潔, 仇金榮, 等.上皮間質轉化分子標記物在乳腺浸潤性導管癌組織中的表達及臨床意義.臨床腫瘤學雜志, 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. 蘇書娟, 邢魯奇, 陳登庭, 等. MMP-2、MMP-9在乳腺導管癌中表達及意義.中國公共衛生, 2011, 27(3):268-270.
24. 朱之坤, 劉志容, 吳誠義. MMP-3與乳腺癌上皮間質轉化的關系及其意義.生命科學研究, 2012, 16(1):63-67.
25. 劉志容, 吳誠義. MMP-3、Vimentin聯合檢測與乳腺癌侵襲轉移的關系.腫瘤防治研究, 2012, 39(2):222-224.
26. 王鳳琴. Twist、E-cadherin蛋白在乳腺良惡性病變中的表達與EMT的關系及其意義.醫學臨床研究, 2011, 28(10):1864-1867.
27. 祝立和, 盧洪勝, 周凱敏, 等. STAT3蛋白激活與乳腺浸潤性導管癌上皮間質轉化的相關性研究.中國現代醫生, 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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