DOI QR코드

DOI QR Code

Immunohistochemical Assessment of E-cadherin and β-catenin in the Histological Differentiations of Oral Squamous Cell Carcinoma

  • Zaid, Khaled Waleed
  • Published : 2014.11.06

Abstract

The aim of this study was to establish the expression and localization of E-cadherin and ${\beta}$-catenin in oral squamous cell carcinomas (OSCC) so that we could correlate the findings with prognostic-relevant histopathological variables. E-cadherin and ${\beta}$-catenin expression in normal oral epithelia and in oral squamous cell carcinomas was examined immunohistochemically, and associations with histopathological differentiation and prognosis were then analyzed in 33 patients who had been operated on for OSCC. E-cadherin expression was found in (82%) of the squamous cells of well differentiated OSCC, (61%) of moderately differentiated and (39%) of poorly differentiated. E-cadherin expression was significantly associated with histological grade (p=0.000). No nuclear staining was detected. In (19.5%) of the cells E-cadherin localized in the cytoplasm, with no correlation to the histological grade (p=0.106). ${\beta}$-Catenin expression was found in 87% of the squamous cells of well differentiated OSCC, 67% of moderately differentiated and 43% of poorly differentiated, the expression was significantly associated with histological grade (p=0.000). the nuclear ${\beta}$-Catenin expression appeared in 3.3% of the cells and it was correlated to the histological grade (p=0.000). In (23.5%) of the cells ${\beta}$-Catenin localized in the cytoplasm, with correlation to the histological grade (p=0.002). According to this study the expression of ${\beta}$-catenin and E-cadherin were independent prognostic factors for histological grade. E-cadherin was closely linked to ${\beta}$-catenin expression in OSCC (p=0.000) and to tumor differentiation. That reflects a structural association and the role of both in tumor progression.

Keywords

Oral squamous cell carcinoma;E-cadherin;${\beta}$-catenin;prognosis

References

  1. Attar E, Dey S, Hablas A, et al (2010). Head and neck cancer in a developing country: a population-based perspective across 8 years. Oral Oncol, 46, 591-6. https://doi.org/10.1016/j.oraloncology.2010.05.002
  2. Ayed-Guerfali DB, Hassairi B, Khabir A, et al (2014). Expression of APC, beta-catenin and E-cadherin in Tunisian patients with gastric adenocarcinoma: clinical significance. Tumour Biol, 35, 1775-83. https://doi.org/10.1007/s13277-013-1236-7
  3. Bagan J, Sarrion G, Jimenez Y (2010). Oral cancer: clinical features. Oral Oncol, 46, 414-7. https://doi.org/10.1016/j.oraloncology.2010.03.009
  4. Bhagat R, Premalata CS, Shilpa V, et al (2013). Altered expression of beta-catenin, E-cadherin, and E-cadherin promoter methylation in epithelial ovarian carcinoma. Tumour Biol, 34, 2459-68. https://doi.org/10.1007/s13277-013-0797-9
  5. Bringuier PP, Umbas R, Schaafsma HE, et al (1993). Decreased E-cadherin immunoreactivity correlates with poor survival in patients with bladder tumors. Cancer Res, 53, 3241-5.
  6. Bienz M (2005). beta-Catenin: a pivot between cell adhesion and Wnt signalling. Curr Biol, 15, R64-7.
  7. Birchmeier W, Weidner KM, Hulsken J, et al (1993). Molecular mechanisms leading to cell junction (cadherin) deficiency in invasive carcinomas. Semin Cancer Biol, 4, 231-9.
  8. Brembeck FH, Rosario M, Birchmeier W (2006). Balancing cell adhesion and Wnt signaling, the key role of beta-catenin. Curr Opin Genet Dev, 16, 51-9. https://doi.org/10.1016/j.gde.2005.12.007
  9. Bruun J, Kolberg M, Nesland JM, et al (2014). Prognostic Significance of beta-catenin, E-cadherin, and SOX9 in colorectal cancer: results from a large populationrepresentative series. Front Oncol, 4, 118.
  10. Cadigan KM, Nusse R (1997). Wnt signaling: a common theme in animal development. Genes Dev, 11, 3286-305. https://doi.org/10.1101/gad.11.24.3286
  11. Chan SW, Kallarakkal TG, Abraham MT (2014). Changed expression of E-cadherin and galectin-9 in oral squamous cell carcinomas but lack of potential as prognostic markers. Asian Pac J Cancer Prev, 15, 2145-52. https://doi.org/10.7314/APJCP.2014.15.5.2145
  12. Deng QW, He BS, Pan YQ, et al (2014). Roles of E-cadherin (CDH1) genetic variationin cancer risk: a meta-analysis. Asian Pac J Cancer Prev, 15, 3705-13. https://doi.org/10.7314/APJCP.2014.15.8.3705
  13. Ebert MP, Yu J, Hoffmann J, et al (2003). Loss of beta-catenin expression in metastatic gastric cancer. J Clin Oncol, 21, 1708-14. https://doi.org/10.1200/JCO.2003.10.017
  14. Fadare O, Reddy H, Wang J, et al (2005). E-cadherin and betacatenin expression in early stage cervical carcinoma: a tissue microarray study of 147 cases. World J Surg Oncol, 3, 38. https://doi.org/10.1186/1477-7819-3-38
  15. Gall TM, Frampton AE (2013). Gene of the month: E-cadherin (CDH1). J Clin Pathol, 66, 928-32. https://doi.org/10.1136/jclinpath-2013-201768
  16. Hu T, Li C (2010). Convergence between Wnt-beta-catenin and EGFR signaling in cancer. Mol Cancer, 9, 236.
  17. Giepmans BN, van Ijzendoorn SC (2009). Epithelial cell-cell junctions and plasma membrane domains. Biochim Biophys Acta, 1788, 820-31. https://doi.org/10.1016/j.bbamem.2008.07.015
  18. Harris TJ, Peifer M (2005). Decisions, decisions: beta-catenin chooses between adhesion and transcription. Trends Cell Biol, 15, 234-7. https://doi.org/10.1016/j.tcb.2005.03.002
  19. Hsu PK, Li AF, Wang YC, et al (2008). Reduced membranous beta-catenin protein expression is associated with metastasis and poor prognosis in squamous cell carcinoma of the esophagus. J Thorac Cardiovasc Surg, 135, 1029-35. https://doi.org/10.1016/j.jtcvs.2007.11.007
  20. Kanczuga-Koda L, Wincewicz A, Fudala A, et al (2014). E-cadherin and beta-catenin adhesion proteins correlate positively with connexins in colorectal cancer. Oncol Lett, 7, 1863-70.
  21. Koay MH, Crook M, Stewart CJ (2012). Cyclin D1, E-cadherin and beta-catenin expression in FIGO Stage IA cervical squamous carcinoma: diagnostic value and evidence for epithelial-mesenchymal transition. Histopathology, 61, 1125-33. https://doi.org/10.1111/j.1365-2559.2012.04326.x
  22. Koinuma N (2010). Economic burden of cancer patients undergoing oral chemotherapy. Gan To Kagaku Ryoho, 37, 1230-3.
  23. Kraus C, Liehr T, Hulsken J, et al (1994). Localization of the human beta-catenin gene (CTNNB1) to 3p21: a region implicated in tumor development. Genomics, 23, 272-4. https://doi.org/10.1006/geno.1994.1493
  24. Krishna A, Singh R, Singh S, et al (2014). Demographic risk factors, affected anatomical sites and clinicopathological profile for oral squamous cell carcinoma in a north Indian population. Asian Pac J Cancer Prev, 15, 6755-60. https://doi.org/10.7314/APJCP.2014.15.16.6755
  25. Lopes FF, da Costa Miguel MC, Pereira AL, et al (2009). Changes in immunoexpression of E-cadherin and betacatenin in oral squamous cell carcinoma with and without nodal metastasis. Ann Diagn Pathol, 13, 22-9. https://doi.org/10.1016/j.anndiagpath.2008.07.006
  26. Laxmidevi LB, Angadi PV, Pillai RK, et al (2010). Aberrant beta-catenin expression in the histologic differentiation of oral squamous cell carcinoma and verrucous carcinoma: an immunohistochemical study. J Oral Sci, 52, 633-40. https://doi.org/10.2334/josnusd.52.633
  27. Liu LK, Jiang XY, Zhou XX, et al (2010). Upregulation of vimentin and aberrant expression of E-cadherin/beta-catenin complex in oral squamous cell carcinomas: correlation with the clinicopathological features and patient outcome. Mod Pathol, 23, 213-24. https://doi.org/10.1038/modpathol.2009.160
  28. Lloreta-Trull J, Munne A, Marinoso ML, et al (2001). Intercellular junctions, apical differentiation, and infiltrative features in colon cancer: an ultrastructural study. the colon cancer team at IMAS. Ultrastruct Pathol, 25, 289-94. https://doi.org/10.1080/019131201753136304
  29. MacDonald BT, Tamai K, He X (2009). Wnt/beta-catenin signaling: components, mechanisms, and diseases. Dev Cell, 17, 9-26. https://doi.org/10.1016/j.devcel.2009.06.016
  30. Ohene-Abuakwa Y, Noda M, Perenyi M, et al (2000). Expression of the E-cadherin/catenin (alpha-, beta-, and gamma-) complex correlates with the macroscopic appearance of early gastric cancer. J Pathol, 192, 433-9. https://doi.org/10.1002/1096-9896(2000)9999:9999<::AID-PATH723>3.0.CO;2-V
  31. Ougolkov A, Yamashita K, Bilim V, et al (2003). Abnormal expression of E-cadherin, beta-catenin, and c-erbB-2 in advanced gastric cancer: its association with liver metastasis. Int J Colorectal Dis, 18, 160-6.
  32. Oyama T, Kanai Y, Ochiai A, et al (1994). A truncated betacatenin disrupts the interaction between E-cadherin and alpha-catenin: a cause of loss of intercellular adhesiveness in human cancer cell lines. Cancer Res, 54, 6282-7.
  33. Petti S (2009). Lifestyle risk factors for oral cancer. Oral Oncol, 45, 340-50. https://doi.org/10.1016/j.oraloncology.2008.05.018
  34. Palacios J, Benito N, Pizarro A, et al (1995). Anomalous expression of P-cadherin in breast carcinoma. correlation with E-cadherin expression and pathological features. Am J Pathol, 146, 605-12.
  35. Pang H, Lu H, Song H, et al (2013). Prognostic values of osteopontin-c, E-cadherin and beta-catenin in breast cancer. Cancer Epidemiol, 37, 985-92. https://doi.org/10.1016/j.canep.2013.08.005
  36. Pannone G, Santoro A, Feola A, et al (2013). The role of E-Cadherin down-regulation in oral cancer: Cdh1 gene expression and epigenetic blockage. Curr Cancer Drug Targets. [Epub ahead of print].
  37. Pukkila MJ, Virtaniemi JA, Kumpulainen EJ, et al (2001). Nuclear beta catenin expression is related to unfavourable outcome in oropharyngeal and hypopharyngeal squamous cell carcinoma. J Clin Pathol, 54, 42-7. https://doi.org/10.1136/jcp.54.1.42
  38. Purcell R, Childs M, Maibach R, et al (2011). HGF/c-Met related activation of beta-catenin in hepatoblastoma. J Exp Clin Cancer Res, 30, 96. https://doi.org/10.1186/1756-9966-30-96
  39. Rodrigo JP, Dominguez F, Suarez V, et al (2007). Focal adhesion kinase and E-cadherin as markers for nodal metastasis in laryngeal cancer. Arch Otolaryngol Head Neck Surg, 133, 145-50. https://doi.org/10.1001/archotol.133.2.145
  40. Rosado P, Lequerica-Fernandez P, Fernandez S, et al (2013). E-cadherin and beta-catenin expression in well-differentiated and moderately-differentiated oral squamous cell carcinoma: relations with clinical variables. Br J Oral Maxillofac Surg, 51, 149-56. https://doi.org/10.1016/j.bjoms.2012.03.018
  41. Shah JP, Gil Z (2009). Current concepts in management of oral cancer--surgery. Oral Oncol, 45, 394-401. https://doi.org/10.1016/j.oraloncology.2008.05.017
  42. Shen CH, Wu JD, Jou YC, et al (2011). The correlation between TWIST, E-cadherin, and beta-catenin in human bladder cancer. J BUON, 16, 733-7.
  43. Valagussa P, Bonadonna G, Veronesi U (1978). Patterns of relapse and survival following radical mastectomy. analysis of 716 consecutive patients. Cancer, 41, 1170-8. https://doi.org/10.1002/1097-0142(197803)41:3<1170::AID-CNCR2820410355>3.0.CO;2-I
  44. Taskin S, Dunder I, Erol E, et al (2012). Roles of E-cadherin and cyclooxygenase enzymes in predicting different survival patterns of optimally cytoreduced serous ovarian cancer patients. Asian Pac J Cancer Prev, 13, 5715-9. https://doi.org/10.7314/APJCP.2012.13.11.5715
  45. Tetsu O, McCormick F (1999). Beta-catenin regulates expression of cyclin D1 in colon carcinoma cells. Nature, 398, 422-6. https://doi.org/10.1038/18884
  46. Umemura K, Takagi S, Shimada T, et al (2013). Prognostic and diagnostic significance of tumor budding associated with beta-catenin expression in submucosal invasive colorectal carcinoma. Tohoku J Exp Med, 229, 53-9. https://doi.org/10.1620/tjem.229.53
  47. Van Aken J, Cuvelier CA, De Wever N, et al (1993). Immunohistochemical analysis of E-cadherin expression in human colorectal tumours. Pathol Res Pract, 189, 975-8. https://doi.org/10.1016/S0344-0338(11)80667-9
  48. van Oort IM, Tomita K, van Bokhoven A, et al (2007). The prognostic value of E-cadherin and the cadherin-associated molecules alpha-, beta-, gamma-catenin and p120ctn in prostate cancer specific survival: a long-term follow-up study. Prostate, 67, 1432-8. https://doi.org/10.1002/pros.20626
  49. Weis WI, Nelson WJ (2006). Re-solving the cadherin-cateninactin conundrum. J Biol Chem, 281, 35593-7. https://doi.org/10.1074/jbc.R600027200
  50. Wheelock MJ, Jensen PJ (1992). Regulation of keratinocyte intercellular junction organization and epidermal morphogenesis by E-cadherin. J Cell Biol, 117, 415-25. https://doi.org/10.1083/jcb.117.2.415
  51. Xu L, Jiang Y, Zheng J, et al (2013). Aberrant expression of betacatenin and E-cadherin is correlated with poor prognosis of nasopharyngeal cancer. Hum Pathol, 44, 1357-64. https://doi.org/10.1016/j.humpath.2012.10.025
  52. Zhai JW, Yang XG, Yang FS, et al (2010). Expression and clinical significance of Ezrin and E-cadherin in esophageal squamous cell carcinoma. Chin J Cancer, 29, 317-20. https://doi.org/10.5732/cjc.009.10505
  53. Yoshii T, Miyagi Y, Nakamura Y, et al (2013). Pilot research for the correlation between the expression pattern of E-cadherinbeta-catenin complex and lymph node metastasis in early gastric cancer. Tumori, 99, 234-8.
  54. Yu Z, Weinberger PM, Provost E, et al (2005). beta-Catenin functions mainly as an adhesion molecule in patients with squamous cell cancer of the head and neck. Clin Cancer Res, 11, 2471-7. https://doi.org/10.1158/1078-0432.CCR-04-2199
  55. Zeng R, Duan L, Kong YK, et al (2014). Prognostic significance of beta-catenin expression in patients with esophageal carcinoma: a meta-analysis. Asian Pac J Cancer Prev, 15, 6103-8. https://doi.org/10.7314/APJCP.2014.15.15.6103

Cited by

  1. β-Catenin Alterations in Squamous Cell Carcinoma of the Lip vol.16, pp.13, 2015, https://doi.org/10.7314/APJCP.2015.16.13.5187
  2. Roles of Signaling Pathways in the Epithelial-Mesenchymal Transition in Cancer vol.16, pp.15, 2015, https://doi.org/10.7314/APJCP.2015.16.15.6201
  3. Recombinant Human Bone Morphogenetic Protein-2 in Development and Progression of Oral Squamous Cell Carcinoma vol.17, pp.3, 2016, https://doi.org/10.7314/APJCP.2016.17.3.927