• 1. 南京大學醫(yī)學院附屬鼓樓醫(yī)院普外科（江蘇南京 210008）;;
  • 2. 南京大學醫(yī)學院附屬鼓樓醫(yī)院醫(yī)學信息科（江蘇南京 210008）;;
  • 3. 南京大學醫(yī)學院附屬鼓樓醫(yī)院病理科（江蘇南京　210008）;

目的 　探討緊密連接蛋白claudin-1在乳腺腫瘤組織中的表達及其與乳腺癌發(fā)生、發(fā)展的關系。
方法　 應用組織芯片技術和免疫組織化學法研究89例乳腺癌和37例乳腺良性病變中claudin-1的表達情況，并統計分析其與乳腺癌淋巴結轉移、TNM分期和腫塊最大徑以及組織學分級間的關系。
結果 　claudin-1在乳腺癌組織中的表達強度明顯弱于乳腺良性病變者（χ2=19.20，P=0.000 2）。在有淋巴結轉移的乳腺癌組織中claudin-1表達強度明顯弱于無淋巴結轉移者（χ2=3.85，P=0.049 7）；TNM分期為Ⅲ期的乳腺癌組織中claudin-1表達強度分別弱于Ⅰ期（χ2=5.29，P=0.021 4）和Ⅱ期（χ2=7.46，P=0.006 3）。claudin-1表達強度在腫塊最大徑各組間（χ2=1.58，P=0.453 8）及組織學各分級之間（χ2=1.02，P=0.600 5）比較差異均無統計學意義。
結論 　乳腺癌的發(fā)生、發(fā)展及轉移可能與claudin-1的表達強度有關，可作為判斷乳腺癌淋巴結轉移和估計預后的參考指標之一。

引用本文： 莊曉明,曹永暉,樊祥山,吳鴻雁. 緊密連接蛋白claudin-1 與乳腺腫瘤的相關性研究. 中國普外基礎與臨床雜志, 2012, 19(2): 192-196. doi: 復制

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. 楊莊青,黃云超,鄒天寧,等． E-cadherin、claudin-1聯合檢測與乳腺癌侵襲轉移關系的研究[ J]．現代腫瘤醫(yī)學 , 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]吳瓊 ,吳曉艷，張海英 ,等．緊密連接蛋白 claudin-6在人乳腺and 3-an auxiliary tool in predicting behavior of mucoepidermoid 癌細胞和組織中的表達及其與乳腺癌淋巴結轉移的關系[ J]．carcinoma of salivary gland origin[J]．Virchows Arch, 2011, 吉林大學學報 (醫(yī)學版 ), 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. 吳瓊, 吳曉艷，張海英, 等．緊密連接蛋白claudin-6 在人乳腺癌細胞和組織中的表達及其與乳腺癌淋巴結轉移的關系 [J]．吉林大學學報( 醫(yī)學版), 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. 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. 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. 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. 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. 5. Swisshelm K，Macek R, Kubbies M．Role of claudins in tumorigenesis[J]．Adv Drug Deliv Rev, 2005, 57(6)：919-928．.
  6. 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. 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. 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. 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. 10. 楊莊青,黃云超,鄒天寧,等． E-cadherin、claudin-1聯合檢測與乳腺癌侵襲轉移關系的研究[ J]．現代腫瘤醫(yī)學 , 2008, 89(11)：1904-1906．.
  11. 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. 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. 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. 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. 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. 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. 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. 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. 19. Aro K, Rosa LE，Bello IO, et al．Expression pattern of claudins 1 [24]吳瓊 ,吳曉艷，張海英 ,等．緊密連接蛋白 claudin-6在人乳腺and 3-an auxiliary tool in predicting behavior of mucoepidermoid 癌細胞和組織中的表達及其與乳腺癌淋巴結轉移的關系[ J]．carcinoma of salivary gland origin[J]．Virchows Arch, 2011, 吉林大學學報 (醫(yī)學版 ), 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. 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. 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. 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. 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. 24. 吳瓊, 吳曉艷，張海英, 等．緊密連接蛋白claudin-6 在人乳腺癌細胞和組織中的表達及其與乳腺癌淋巴結轉移的關系 [J]．吉林大學學報( 醫(yī)學版), 2008, 34(2)：274-277, 357．.
  25. 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. 26. Martin TA, Mason MD, Jiang WG．Tight junctions in cancer metastasis [J]．Front Biosci, 2011, 16：898-936．.