Study on Correlation Between Tight Junction Protein Claudin-1 and Breast Neoplasms_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

ZHUANG Xiaoming ¹ , CAO Yonghui ² , FAN Xiangshan ³ , WU Hongyan ³

1. Department of General Surgery， Affiliated Drum Tower Hospital，Nanjing University Medical College， Nanjing 210008， Jiangsu Province， China;;
2.Department of Medical Information，Affiliated Drum Tower Hospital， Nanjing University Medical College， Nanjing 210008， Jiangsu Province， China;;
3.Department of Pathology， Affiliated Drum Tower Hospital， Nanjing University Medical College， Nanjing 210008，Jiangsu Province， China;

Corresponding author：

Keywords：

Breast neoplasm; Lymph node metastasis; Tight junction protein; Claudin-1

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Objective 　To investigate the expression of claudin-1 in breast tumor tissues and the relationship of development and progress of breast neoplasm．
Methods 　The expressions of claudin-1 in 89 cases of breast cancer and 37 benign breast diseases were tested by tissue chip technology and immunohistochemistry．The relationships of claudin-1 expression to the lymph node metastasis，TNM staging，maximum diameter of the tumor，and histology grade were statistically analyzed．
Results 　The expression of claudin-1 in the breast cancer was significantly lower than that in the benign breast disease（χ2=19.20，P=0.000 2）．The claudin-1 expression in the patients with lymph node metastasis was significantly lower than that without lymph node metastasis （χ2=3.85，P=0.049 7）．The claudin-1 expression in the stageⅢ of TNM staging was weaker than that in the stage Ⅰ（χ2=5.29，P=0.021 4） and stage Ⅱ （χ2=7.46，P=0.006 3），respectively. There was no significant difference of the claudin-1 expression in the different maximum diameters of tumor （χ2=1.58，P=0.453 8） or histology grades （χ2=1.02，P=0.600 5），respectively．
Conclusions 　 The expression of claudin-1 might be correlated with the occurrence，development，and metastasis in breast tumor．It may be one of the potential indicator for lymph node metastasis and prognosis assessment in breast cancer．

Citation： ZHUANG Xiaoming,CAO Yonghui,FAN Xiangshan,WU Hongyan. Study on Correlation Between Tight Junction Protein Claudin-1 and Breast Neoplasms. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2012, 19(2): 192-196. doi: Copy

1.	Myal Y, Leygue E, Blanchard AA．Claudin 1 in breast tumorigenesis：revelation of a possible novel “claudin high” subset of breast cancers[J]．J Biomed Biotechnol, 2010, 2010：956897．.
2.	Blanchard AA, Skliris GP, Watson PH, et al．Claudins 1, 3, and 4 protein expression in ER negative breast cancer correlates with markers of the basal phenotype[J]．Virchows Arch, 2009, 454(6)：647-656．.
3.	Escudero-Esparza A, Jiang WG，Martin TA．The Claudin family and its role in cancer and metastasis[J]．Front Biosci, 2011, 16：1069-1083．.
4.	Sheehan GM, Kallakury BV, Sheehan CE，et al．Loss of claudins-1 and -7 and expression of claudins-3 and -4 correlate with prognostic variables in prostatic adenocarcinomas[J]．Hum Pathol, 2007, 38(4)：564-569．.
5.	Swisshelm K，Macek R, Kubbies M．Role of claudins in tumorigenesis[J]．Adv Drug Deliv Rev, 2005, 57(6)：919-928．.
6.	Cohn ML, Goncharuk VN, Diwan AH, et al．Loss of claudin-1 expression in tumor-associated vessels correlates with acquisition of metastatic phenotype in melanocytic neoplasms[J]．J Cutan Pathol, 2005, 32(8)：533-536．.
7.	Sobel G, Németh J, Kiss A, et al．Claudin 1 differentiates endometrioid and serous papillary endometrial adenocarcinoma[J]． Gynecol Oncol, 2006，103(2)：591-598．.
8.	Chao YC, Pan SH, Yang SC, et al．Claudin-1 is a metastasis suppressor and correlates with clinical outcome in lung adenocarcinoma[J]．Am J Respir Crit Care Med，2009, 179(2)：123-133.
9.	Miyamoto K, Kusumi T, Sato F，et al．Decreased expression of claudin-1 is correlated with recurrence status in esophageal squamous cell carcinoma[J]．Biomed Res, 2008, 29(2)：71-76．.
10.	杨庄青,黄云超,邹天宁,等． E-cadherin、claudin-1联合检测与乳腺癌侵袭转移关系的研究[ J]．现代肿瘤医学 , 2008, 89(11)：1904-1906．.
11.	Tokés AM, Kulka J, Paku S, et al．Claudin-1, -3 and -4 proteins and mRNA expression in benign and malignant breast lesions：a research study[J]．Breast Cancer Res, 2005, 7(2)：R296-R305.
12.	Szasz AM, Tokes AM, Micsinai M, et al．Prognostic significance of claudin expression changes in breast cancer with regional lymph node metastasis[J]．Clin Exp Metastasis, 2011，28(1)：55-63．.
13.	Dhawan P, Singh AB, Deane NG, et al．Claudin-1 regulates cellular transformation and metastatic behavior in colon cancer[J]． J Clin Invest, 2005, 115(7)：1765-1776．.
14.	Szabó I, Kiss A, Schaff Z, et al．Claudins as diagnostic and prognostic markers in gynecological cancer[J]．Histol Histopathol, 2009，24(12)：1607-1615．.
15.	Lee JW, Hsiao WT, Chen HY, et al．Upregulated claudin-1 expression confers resistance to cell death of nasopharyngeal carcinoma cells[J]．Int J Cancer, 2010, 126(6)：1353-1366．.
16.	Hsueh C，Chang YS, Tseng NM, et al．Expression pattern and prognostic significance of claudins 1, 4, and 7 in nasopharyngeal carcinoma[J]．Hum Pathol，2010, 41(7)：944-950．.
17.	Kleinberg L, Holth A, Trope CG, et al．Claudin upregulation in ovarian carcinoma effusions is associated with poor survival[J]． carcinomas[J]．Clin Cancer Res, 2008，14(21)：7035-7042．Hum Pathol，2008, 39(5)：747-757．[22] Kulawiec M, SafinaA, Desouki MM, et al．Tumorigenic transfor.
18.	Oku N, Sasabe E, Ueta E, et al．Tight junction protein claudin-1 mation of human breast epithelial cells induced by mitochondrial enhances the invasive activity of oral squamous cell carcinoma DNA depletion[J]．Cancer Biol Ther, 2008, 7(11)：1732-1743.cells by promoting cleavage of laminin-5 γ2 chain via matrix me-[23] Hoevel T，Macek R, Swisshelm K, et al．Reexpression of the TJ talloproteinase (MMP)-2 and membrane-type MMP-1 [J]．Can-protein CLDN1 induces apoptosis in breast tumor spheroids[J]． cer Res, 2006, 66(10)：5251-5257．Int J Cancer, 2004, 108(3)：374-383．.
19.	Aro K, Rosa LE，Bello IO, et al．Expression pattern of claudins 1 [24]吴琼 ,吴晓艳，张海英 ,等．紧密连接蛋白 claudin-6在人乳腺and 3-an auxiliary tool in predicting behavior of mucoepidermoid 癌细胞和组织中的表达及其与乳腺癌淋巴结转移的关系[ J]．carcinoma of salivary gland origin[J]．Virchows Arch, 2011, 吉林大学学报 (医学版 ), 2008, 34(2)：274-277, 357．458(3)：341-348．[25] Soini Y．Expression of claudins 1, 2, 3, 4, 5 and 7 in various types.
20.	Coutinho-Camillo CM, Louren.o SV, da Fonseca FP, et al．Clau-of tumours[J]．Histopathology, 2005, 46(5)：551-560．din expression is dysregulated in prostate denocarcinomas but [26] Martin TA, Mason MD, Jiang WG．Tight junctions in cancer me-does not correlate with main clinicopathological parameters[J]． tastasis[J]．Front Biosci, 2011, 16：898-936． Pathology，2011, 43(2)：143-148．.
21.	Fritzsche FR, Oelrich B, Johannsen M, et al．Claudin-1 protein expression is a prognostic marker of patient survival in renal cell carcinomas [J]．Clin Cancer Res, 2008，14(21)：7035-7042．.
22.	Kulawiec M, Safina A, Desouki MM, et al．Tumorigenic transformation of human breast epithelial cells induced by mitochondrial DNA depletion [J]．Cancer Biol Ther, 2008, 7(11)：1732-1743.
23.	Hoevel T，Macek R, Swisshelm K, et al．Reexpression of the TJ protein CLDN1 induces apoptosis in breast tumor spheroids [J]．Int J Cancer, 2004, 108(3)：374-383．.
24.	吴琼, 吴晓艳，张海英, 等．紧密连接蛋白claudin-6 在人乳腺癌细胞和组织中的表达及其与乳腺癌淋巴结转移的关系 [J]．吉林大学学报( 医学版), 2008, 34(2)：274-277, 357．.
25.	Soini Y．Expression of claudins 1, 2, 3, 4, 5 and 7 in various types of tumours [J]．Histopathology, 2005, 46(5)：551-560．.
26.	Martin TA, Mason MD, Jiang WG．Tight junctions in cancer metastasis [J]．Front Biosci, 2011, 16：898-936．.

1. Myal Y, Leygue E, Blanchard AA．Claudin 1 in breast tumorigenesis：revelation of a possible novel “claudin high” subset of breast cancers[J]．J Biomed Biotechnol, 2010, 2010：956897．.
2. Blanchard AA, Skliris GP, Watson PH, et al．Claudins 1, 3, and 4 protein expression in ER negative breast cancer correlates with markers of the basal phenotype[J]．Virchows Arch, 2009, 454(6)：647-656．.
3. Escudero-Esparza A, Jiang WG，Martin TA．The Claudin family and its role in cancer and metastasis[J]．Front Biosci, 2011, 16：1069-1083．.
4. Sheehan GM, Kallakury BV, Sheehan CE，et al．Loss of claudins-1 and -7 and expression of claudins-3 and -4 correlate with prognostic variables in prostatic adenocarcinomas[J]．Hum Pathol, 2007, 38(4)：564-569．.
5. Swisshelm K，Macek R, Kubbies M．Role of claudins in tumorigenesis[J]．Adv Drug Deliv Rev, 2005, 57(6)：919-928．.
6. Cohn ML, Goncharuk VN, Diwan AH, et al．Loss of claudin-1 expression in tumor-associated vessels correlates with acquisition of metastatic phenotype in melanocytic neoplasms[J]．J Cutan Pathol, 2005, 32(8)：533-536．.
7. Sobel G, Németh J, Kiss A, et al．Claudin 1 differentiates endometrioid and serous papillary endometrial adenocarcinoma[J]． Gynecol Oncol, 2006，103(2)：591-598．.
8. Chao YC, Pan SH, Yang SC, et al．Claudin-1 is a metastasis suppressor and correlates with clinical outcome in lung adenocarcinoma[J]．Am J Respir Crit Care Med，2009, 179(2)：123-133.
9. Miyamoto K, Kusumi T, Sato F，et al．Decreased expression of claudin-1 is correlated with recurrence status in esophageal squamous cell carcinoma[J]．Biomed Res, 2008, 29(2)：71-76．.
10. 杨庄青,黄云超,邹天宁,等． E-cadherin、claudin-1联合检测与乳腺癌侵袭转移关系的研究[ J]．现代肿瘤医学 , 2008, 89(11)：1904-1906．.
11. Tokés AM, Kulka J, Paku S, et al．Claudin-1, -3 and -4 proteins and mRNA expression in benign and malignant breast lesions：a research study[J]．Breast Cancer Res, 2005, 7(2)：R296-R305.
12. Szasz AM, Tokes AM, Micsinai M, et al．Prognostic significance of claudin expression changes in breast cancer with regional lymph node metastasis[J]．Clin Exp Metastasis, 2011，28(1)：55-63．.
13. Dhawan P, Singh AB, Deane NG, et al．Claudin-1 regulates cellular transformation and metastatic behavior in colon cancer[J]． J Clin Invest, 2005, 115(7)：1765-1776．.
14. Szabó I, Kiss A, Schaff Z, et al．Claudins as diagnostic and prognostic markers in gynecological cancer[J]．Histol Histopathol, 2009，24(12)：1607-1615．.
15. Lee JW, Hsiao WT, Chen HY, et al．Upregulated claudin-1 expression confers resistance to cell death of nasopharyngeal carcinoma cells[J]．Int J Cancer, 2010, 126(6)：1353-1366．.
16. Hsueh C，Chang YS, Tseng NM, et al．Expression pattern and prognostic significance of claudins 1, 4, and 7 in nasopharyngeal carcinoma[J]．Hum Pathol，2010, 41(7)：944-950．.
17. Kleinberg L, Holth A, Trope CG, et al．Claudin upregulation in ovarian carcinoma effusions is associated with poor survival[J]． carcinomas[J]．Clin Cancer Res, 2008，14(21)：7035-7042．Hum Pathol，2008, 39(5)：747-757．[22] Kulawiec M, SafinaA, Desouki MM, et al．Tumorigenic transfor.
18. Oku N, Sasabe E, Ueta E, et al．Tight junction protein claudin-1 mation of human breast epithelial cells induced by mitochondrial enhances the invasive activity of oral squamous cell carcinoma DNA depletion[J]．Cancer Biol Ther, 2008, 7(11)：1732-1743.cells by promoting cleavage of laminin-5 γ2 chain via matrix me-[23] Hoevel T，Macek R, Swisshelm K, et al．Reexpression of the TJ talloproteinase (MMP)-2 and membrane-type MMP-1 [J]．Can-protein CLDN1 induces apoptosis in breast tumor spheroids[J]． cer Res, 2006, 66(10)：5251-5257．Int J Cancer, 2004, 108(3)：374-383．.
19. Aro K, Rosa LE，Bello IO, et al．Expression pattern of claudins 1 [24]吴琼 ,吴晓艳，张海英 ,等．紧密连接蛋白 claudin-6在人乳腺and 3-an auxiliary tool in predicting behavior of mucoepidermoid 癌细胞和组织中的表达及其与乳腺癌淋巴结转移的关系[ J]．carcinoma of salivary gland origin[J]．Virchows Arch, 2011, 吉林大学学报 (医学版 ), 2008, 34(2)：274-277, 357．458(3)：341-348．[25] Soini Y．Expression of claudins 1, 2, 3, 4, 5 and 7 in various types.
20. Coutinho-Camillo CM, Louren.o SV, da Fonseca FP, et al．Clau-of tumours[J]．Histopathology, 2005, 46(5)：551-560．din expression is dysregulated in prostate denocarcinomas but [26] Martin TA, Mason MD, Jiang WG．Tight junctions in cancer me-does not correlate with main clinicopathological parameters[J]． tastasis[J]．Front Biosci, 2011, 16：898-936． Pathology，2011, 43(2)：143-148．.
21. Fritzsche FR, Oelrich B, Johannsen M, et al．Claudin-1 protein expression is a prognostic marker of patient survival in renal cell carcinomas [J]．Clin Cancer Res, 2008，14(21)：7035-7042．.
22. Kulawiec M, Safina A, Desouki MM, et al．Tumorigenic transformation of human breast epithelial cells induced by mitochondrial DNA depletion [J]．Cancer Biol Ther, 2008, 7(11)：1732-1743.
23. Hoevel T，Macek R, Swisshelm K, et al．Reexpression of the TJ protein CLDN1 induces apoptosis in breast tumor spheroids [J]．Int J Cancer, 2004, 108(3)：374-383．.
24. 吴琼, 吴晓艳，张海英, 等．紧密连接蛋白claudin-6 在人乳腺癌细胞和组织中的表达及其与乳腺癌淋巴结转移的关系 [J]．吉林大学学报( 医学版), 2008, 34(2)：274-277, 357．.
25. Soini Y．Expression of claudins 1, 2, 3, 4, 5 and 7 in various types of tumours [J]．Histopathology, 2005, 46(5)：551-560．.
26. Martin TA, Mason MD, Jiang WG．Tight junctions in cancer metastasis [J]．Front Biosci, 2011, 16：898-936．.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Study on Correlation Between Tight Junction Protein Claudin-1 and Breast Neoplasms

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