Reduced Expression of E-cadherin in Human Non-small Cell Lung Carcinoma

Myong, Na-Hye

  • Published : 20040000

Abstract

Purpose: E-cadherin, a calcium-dependent cell to cell adhesion molecule, plays a key role in the maintenance of tissue integrity. Reduction or loss of E-cadherin has been reported to have a role in the development of human malignancies. The expression of E-cadherin was analyzed in human non-small cell lung carcinoma (NSCLC) to elucidate the role in pulmonary carcinogenesis and determine the relationship with several clinicopathological factors and the prognosis. Materials and Methids: Sixty five human cases of NSCLC were evaluated by immunohistochemical analysis for the expression of E-cadherin. The immunostaining results for E-cadherin were semiquantitatively interpreted, as preserved and reduced, in the tumor tissues. The E-cadherin expression was analyzed in relation to several clinicopathological data and the survival. The cell proliferation index of the tumors was evaluated by immunostaining with the Ki-67 antigen. Results: Reduced E-cadherin expression was found in 51 cases of NSCLC tissues (78.4%) compared to that in the normal controls. Reduced E-cadherin expression was significantly correlated with male smokers and squamous cell type of the cancer, but not with histological grade, TNM stage and survival. The E-cadherin expression showed a weak inverse relationship with the proliferative activity of tumor cells, which was measured using the Ki-67 antigen. Conclusion: Our data support the hypothesis that reduced E-cadherin expression may play a role in the pathogenesis of human NSCLC, which might be associated with the control for cell proliferation.

Keywords

References

  1. Smythe WR, Williams JP, Wheelock MJ, Johnson KR, Kaiser LR, Albelda SM. Cadherin and catenin expression in normal human bronchialepithelium and non-small cell lung cancer. Lung Cancer 1999;24:157-168 https://doi.org/10.1016/S0169-5002(99)00032-X
  2. Takeichi M. Cadherin cell adhesion receptors as a morphogenetic regulator. Science 1991;251:1451-1455 https://doi.org/10.1126/science.2006419
  3. Takeichi M. Cadherins in cancer: implications for invasion and metastasis. Curr Opin Cell Biol 1993;5:806-811 https://doi.org/10.1016/0955-0674(93)90029-P
  4. Nakanishi Y, Ochiai A, Akimoto S, Kato H, Watanabe H, Tachimori Y, Yamamoto S, Hirohashi S. Expression of Ecadherin, $\alpha$-catenin, $\beta$-catenin and plakoglobin in esophageal carcinomas and its prognostic significance: immunohistochemical analysis of 96 lesions. Oncology 1997;112:46-54
  5. Gabbert HE, Mueller W, Schneiders A, Meier S, Moll R, Birchmeier W, Hommel G. Prognostic value of E-cadherin expression in 413 gastric carcinomas. Int J Cancer 1996;69:184-189 https://doi.org/10.1002/(SICI)1097-0215(19960621)69:3<184::AID-IJC6>3.0.CO;2-W
  6. Dorudi S, Hanby AM, Poulsom R, Northover J, Hart IR. Level of expression of E-cadherin mRNA in colorectal cancer correlates with clinical outcome. Br J Cancer 1995;71:614-616 https://doi.org/10.1038/bjc.1995.119
  7. Ihara A, Koizumi H, hashizume R, Uchikoshi T. Expression of epithelial cadherin and $\alpha$- and $\beta$-catenin in nontumoral livers and hepatocellular carcinomas. Hepatology 1996;23: 1441-1447
  8. Gunji N, Oda T, Todoroki T, Kanazawa N, Kawamoto T, Yuzawa K, Scarpa A, Fukao K. Pancreatic carcinoma: correlation between E-cadherin and $\alpha$-catenin expression status and liver metastasis. Cancer (Phila.) 1998;82:1649-1656 https://doi.org/10.1002/(SICI)1097-0142(19980501)82:9<1649::AID-CNCR9>3.0.CO;2-5
  9. Cheng L, Nagabhushan M, Pretlow TP, Amini SB, Pretlow TG. Expression of E-cadherin in primary and metastatic prostate cancer. Am J Pathol 1996;148:1375-1380
  10. Fei Q, Zhang H, Chen X, Wang J-C, Zhang R, Xu W, Zhang Z, Zou W, Zhang K, Qi Q, Wang M, Tao S, Luo Z. Defected expression of E-cadherin in non-small cell lung cancer. Lung Cancer 2002;37:147-152 https://doi.org/10.1016/S0169-5002(02)00077-6
  11. Lee Y-C, Wu C-T, Chen C-S, Chang Y-L. E-cadherin expression in surgically-resected non-small cell lung cancers-A clinicopathological study. Thorac Cardiov Surg 2000;48:294-299 https://doi.org/10.1055/s-2000-7885
  12. Kase S, Sugio K, Yamazaki K, Okamoto T, Yano T, Sugimachi K. Expression of E-cadherin and $\beta$-catenin in human non-small cell lung cancer and the clinical significance. Clin Cancer Res 2000;6:4789-4796
  13. Lim S-C, Jang I-G, Kim Y-C, Park K-O. The role of Ecadherin expression in non-small cell lung cancer. J Korean Med Sci 2000;15:501-506 https://doi.org/10.3346/jkms.2000.15.5.501
  14. Liu D, Huang C-l, Kameyama K, Hayashi E, Yamauchi A, Koabyashi S, Yokomise H. E-cadherin expression associated with differentiation and prognosis in patients with non-small cell lung cancer. Ann Thorac Surg 2001;71:949-955 https://doi.org/10.1016/S0003-4975(00)02545-5
  15. Sulzer MA, Leers MPG, van Noord JA, Bollen ECM, Theunissen PHMH. Reduced E-cadherin expression is associated with increased lymph node metastasis and unfavorable prognosis in non-small cell lung cancer. Am J Respir Crit Care Med 1998; 157:1319-1323 https://doi.org/10.1164/ajrccm.157.4.9703099
  16. Shibanuma H, Hirano T, Tsuji K, QingFang W, Shrestha B, Konaka C, Ebihara Y, Kato H. Influence of E-cadherin dysfunction upon local invasion and metastasis in non-small cell lung cancer. Lung Cancer 1998;22:85-95 https://doi.org/10.1016/S0169-5002(98)00053-1
  17. Bohm M, Totzeck B, Wieland I. Differences of E-cadherin expression levels and patterns in human lung cancer. Ann Hematol 1994;68:81-83 https://doi.org/10.1007/BF01715136
  18. Choi YS, Shim YM, Kim S-H, Son DS, Lee H-S, Kim GY, Han J, Kim J. Prognostic significance of E-cadherin and $\beta$- catenin in resected stage I non-small cell lung cancer. Eur J Cardiothorac Surg 2003;24:441-449 https://doi.org/10.1016/S1010-7940(03)00308-7
  19. Bohm M, Totzeck B, Birchmeier W, Wieland I. Differences of E-cadherin expression levels and patterns in primary and metastatic human lung cancer. Clin Exp Metastasis 1994;12:55-62 https://doi.org/10.1007/BF01784334
  20. Oh BR, Nah GJ, Kim SJ, Sim JH, Kwon DD, Park KS, Ryu SB, Park YI. The clinical usefulness of membranous Ecadherin in transitional cell carcinoma of the bladder. J Korean Cancer Assoc 1998;30:1219-1226
  21. Han AC, Peralta-Soler A, Knudsen KA, Wheelock MJ, Johnson KR, Salazar H. Differential expression of N-cadherin in pleural mesotheliomas and E-cadherin in lung adenocarcinomas in formalin-fixed, paraffin-embedded tissues. Hum Pathol 1997;28:641-645 https://doi.org/10.1016/S0046-8177(97)90171-4
  22. Nawrocki B, Polette M, Van Hengel J, Tournier J-M, Van Roy F, Birembaut P. Cytoplasmic redistribution of E-cadherin-catenin adhesion complex is associated with down-regulated tyrosine phosphorylation of E-cadherin in human bronchopulmonary carcinomas. Am J Pathol 1998;153:1521-1530 https://doi.org/10.1016/S0002-9440(10)65740-9
  23. Morton RA, Ewing CM, Nagafuchi A, Tsukita S, Issacs WB. Recution of E- cadherin levels and deletion of the $\alpha$-catenin gene in human prostate cancer cells. Cancer Res 1993;53:3585- 3590
  24. Janowski JA, Newham PM, Kandemir O, Hirano M, Takeichi M, Pignatelli M. Differential expression of E-cadherin in normal, metaplastic and dysplastic oesophageal mucosa: a putative biomarker. Int J Oncol 1993;4:441-448
  25. St Croix B, Sheehan C, Rak JW, Florenes VA, Slingerland JM, Kerbel RS. E-cadherin dependent growth suppression is mediated by the cyclin-dependent kinase inhibitor p27 (KIP1). J Cell Biol 1998;142:557-571 https://doi.org/10.1083/jcb.142.2.557