28May 2018

E-CADHERIN AS A PROGNOSTIC AND PREDICTIVE BIOMARKER IN INVASIVE BREAST CARCINOMA, A CLINICO-PATHOLOGICAL STUDY.

  • Pathology Department, Medical Research Institute, Alexandria University, Alexandria, Egypt.
  • Surgery Department, Medical Research Institute, Alexandria University, Alexandria, Egypt.
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Background: Breast cancer continues to be a major cause of morbidity and mortality in Egypt. The behavior of breast cancer varies widely. Several parameters have been investigated to predict the prognosis in breast cancer. But still there is no single parameter that can predict prognosis in an individual patient. E-cadherin is a novel prognostic marker; a calcium-dependent epithelial cell adhesion molecule. Its loss has been associated with metastases, thereby providing evidence for its role as an invasion suppressor. Aim: The objective of the present study was to assess the prognostic value of E-cadherin expression in breast cancer cases, and its correlations with the other studied prognostic parameters, especially the lymph node status. Materials and methods: the immunohistochemical expression of E-cadherin was studied in 70 cases of invasive breast cancer; ten of them are of the lobular subtype. Results: E-cadherin expression was positive in 44 cases (62.9%) and negative in 26 cases (37.1%). It was positive in 42 cases of the 58 cases of invasive ductal type, while it was negative in all the lobular breast cancer cases and it was positive in both the mucinous and papillary carcinoma. There was a statistically significant difference between E-cadherin positive and E-cadherin negative cases as regard tumor grade and stage, lymph node status, Her2? receptor status and conservative surgery rates while there was no statistically significant difference between E-cadherin+ /- as regard tumor size, Estrogen and Progesterone status. Conclusion: A significant correlation was found between strong E-cadherin expression and node negative cases indicating that E-cadherin can be used as a prognostic and predictive marker.

  1. Ferlay J, Soerjmataram I, Ervik M, Diskshit R, Eser S, Mathers C, et al. GLOBOCAN 2012 v1.0. Cancer Incidence and Mortality Worldwide: IARC Cancer Base No.11. Lion, France: International Agency for Research on Cancer; 2013.
  2. World Health Organization (WHO). The global burden of disease: 2004 update. Geneva, Switzerland: WHO; 2008.
  3. Chouchane L, Boussen H, Sastry KS. Breast cancer in Arab population: molecular characteristics and disease management implication. Lancet Oncol 2013;1 4(10):e417-24.
  4. Azim HA, Ibrahim AS. Breast cancer in Egypt, China and Chinese: statistics and beyond. J Thorac Dis 2014; 6(7):864-6.
  5. Dai X, Li Y, Bai Z, Tang XQ. Molecular portraits revealing the heterogenesityof breast tumor subtypes defined using immunohistochemical markers. Sci Rep 2015;5:14499.
  6. LehmannBD, Bauer JA, Chen X, Sanders ME, Chakravarthy AB, Shyr Y, et al. Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. J Clin Invest 2011;121(7):2750-67.
  7. Gumbiner BM. Cell adhesion: The molecular basis of tissue architecture and morphogenesis. Cell 1996;84:345?57.
  8. Barth AI, Nathke IS, Nelson WJ. Cadherins, catenins and APC protein: interplay between cytoskeletal complexes and signaling pathways. Curr Opin Cell Biol 1997;9:683?90.
  9. Barkan D, Kleinman H, Simmons JL, Asmussen H, Kamaraju AK, Hoenorhoff MJ, et al. Inhibition of metastatic outgrowth from single dormant tumor cells by targeting the cytoskeleton. Cancer Res 2008; 68(15):6241-50.
  10. Niessen CM, Leckband D, Yap AS. Tissue organization by classical cadherin adhesion molecules: dynamic molecular and cellular mechanisms of morphogenetic regulation. Physiol Rev 2011; 91(2):691-731.
  11. Harrison OJ, Jin X, Hong S, Bahna F, Ahlsen G, Brasch J, et al. The extracellular architecture of adherens junctions revealed by crystal structures of type I cadherins. Structure 2011; 19(2):244-56.
  12. Tang VW, Brieher WM. α-actinin-4/FSGS1 is required for Arp2/3-dependent actin assembly at the adherens junction. J Cell Biol 2012; 196(1):115-30.
  13. Kovacs EM, Verma S, Ali RG, Ratheesh A, Hamilton NA, Akhmanova A, et al. N-WASP regulates the epithelial junctional actin cytoskeleton through a non-canonical post-nucleation pathway. Nat Cell Biol 2011; 13(8):934-43.
  14. Helwani FM, Kovacs EM, Paterson AD, Verma S, Ali RG, Fanning AS, et al. Cortactin is necessary for E-cadherin-mediated contact formation and actin reorganization. J Cell Biol 2004; 164:899-910.
  15. Drees F, Pokutta S, Yamada S, Nelson WJ, Weis WI. α-catenin is a molecular switch that binds E-cadherin?β-catenin and regulates actin-filament assembly. Cell 2005; 123:903-15.
  16. Maddugoda MP, Crampton MS, Shewan AM, Yap AS. Myosin VI and vinculin cooperate during the morphogenesis of cadherin cell?cell contacts in mammalian epithelial cells. J Cell Biol 2007; 178: 529?40.
  17. Sousa S, Cabanes D, Bougn?res L, Lecuit M, Sansonetti P, Tran-Van-Nhieu G, et al. Src, cortactin and Arp2/3 complex are required for E-cadherin-mediated internalization of Listeria into cells. Cell Microbiol 2007; 9(11):2629-43.
  18. Berx G, van Roy F. Involvement of members of the cadherin superfamily in cancer. Cold Spring Harb. Perspect Biol 2009; 1; a003129.
  19. Graff JR, Gabrielson E, Fujii H, Baylin SB, Herman JG. Methylation patterns of the E-cadherin 5′ CpG island are unstable and reflect the dynamic, heterogeneous loss of E-cadherin expression during metastatic progression. J Biol Chem 2000; 275:2727?32.
  20. Chao YL, Shepard CR, Wells A. Breast carcinoma cells reexpress E-cadherin during mesenchymal to epithelial reverting transition. Mol Cancer 2010; 9:179.
  21. Kirkpatrick LA, Feeney BC. A simple guide to IBM SPSS statistics for version 20.0. Student ed. Belmont, Calif.: Wadsworth, Cengage Learning; 2013.
  22. Moll R, Mitze M, Birchmeier W. Differential loss of E-cadherin expression in infiltrating ductal and lobular breast carcinomas. Am J Pathol 1993; 143:1731?42.
  23. Howard EM, Lau SK, Lyles RH, Birdsong GG, Umbreit JN, Kochhar R. Expression of e-cadherin in high-risk breast cancer. J Cancer Res Clin Oncol 2005;131(1):14-8.
  24. Gamello C, palacios J, Pizarro A, Cano A. Correlation of E-cadherin expression with differentiation grade and histological type in breast carcinoma. Am J Pathol 1993;142:987?93.
  25. Cowin P, Hastell S. Cadherins and catenins in breast cancer. Curr Opin Cell Biol 2005; 17(5):499?508.
  26. Gillet CE, Miles DW, Ryder K. Retension of the expression of E-cadherin and catenins is associated with shorter survival in grade III ductal carcinoma of the breast. J Pathol 2001; 193:433?41.
  27. Zschiesche W, Sch?nborn I, Behrens J, Herrenknecht K, Hartveit F, Lilleng P, et al. Expression of E-cadherin and catenins in invasive mammary carcinomas. Anticancer Res 1997; 17(1B):561-7.
  28. B?nkfalvi A, Terpe HJ, Breukelmann D, Bier B, Rempe D, Pschadka G, et al. Immunophenotypic and prognostic analysis of E-cadherin and beta-catenin expression during breast carcinogenesis and tumour progression: a comparative study with CD44. Histopathology 1999; 34(1):25-34.
  29. Jankowski JA, Bedford FK, Kim YS. Changes in gene structure and regulation of E-cadherin during epithelial development, differentiation and disease Prog. Nucleic Acid Res Mol Biol 1997 57 187 215
  30. D?Souza B, Taylor J. Over expression of Erbb2 in human mammary epithelial cells signals inhibition of e-cad gene. Proc Nath Acad Sci 1994; 91:7202?6.

[Suzanna William Skander, Hala Khalil Maghraby, Heba Moomen and Ahmed Farouk Alkarmouty. (2018); E-CADHERIN AS A PROGNOSTIC AND PREDICTIVE BIOMARKER IN INVASIVE BREAST CARCINOMA, A CLINICO-PATHOLOGICAL STUDY. Int. J. of Adv. Res. 6 (May). 1444-1451] (ISSN 2320-5407). www.journalijar.com

Ahmed Farouk Al Karmouty
Surgery Department, Medical Research Institute, Alexandria University, Alexandria, Egypt

DOI:

Article DOI: 10.21474/IJAR01/7177      
DOI URL: https://dx.doi.org/10.21474/IJAR01/7177

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