Archives of Gynecology and Obstetrics

, Volume 284, Issue 2, pp 437–443 | Cite as

E-cadherin as a prognostic marker in human serous carcinomas of the ovary: an immunohistochemical analysis

  • Darius Dian
  • Ansgar Brüning
  • Ioannis MylonasEmail author
Gynecologic Oncology



Ovarian cancer is a gynecologic cancer with a high mortality rate, demonstrating the need for effective and reliable tumor markers during the staging and treatment processes.


Expression of E-cadherin was immunohistochemically analyzed in 100 ovarian cancer tissue samples.


A significant association of E-cadherin expression with histological grading (p = 0.001) and surgical stage (p = 0.020) could be demonstrated. However, the staining intensity of E-cadherin was not significantly associated with progression-free, cause-specific survival or overall survival in serous ovarian carcinomas.


The E-cadherin expression was associated with FIGO surgical staging and histological differentiation in serious ovarian carcinomas, suggesting a substantial role in the carcinogenesis of serous ovarian carcinomas. However, although patients with a strong E-cadherin staining intensity had a better prognosis, no statistical significant differences could be observed. Therefore, E-cadherin might not be a useful prognostic tumor marker in serous ovarian carcinomas.


Serous ovarian cancer E-cadherin Immunohistochemistry Prognosis Survival 



We would like to thank Mrs. C. Dannenmann, Mrs. S. Kunze, Mrs. C. Kuhn Dr. N. Shabani, Dr. T. Blankenstein, Dr. A. Burges, Prof. U. Jeschke, and Prof. K. Friese for support in immunohistochemical analysis and the previous characterization of the analyzed ovarian tumor samples. Additionally, we would also like to thank Prof. D. Hölzel—Institute of Medical Informatics, Biometry and Epidemiology, Ludwig-Maximilians-University, Munich, and Mr. M. Schmidt of the Munich Tumor Registry for supplying the survival data.

Conflict of interest



  1. 1.
    Colombo N, Van Gorp T, Parma G, Amant F, Gatta G, Sessa C, Vergote I (2006) Ovarian cancer. Crit Rev Oncol Hematol 60(2):159–179. doi: 10.1016/j.critrevonc.2006.03.004 PubMedCrossRefGoogle Scholar
  2. 2.
    International Agency for Research on Cancer I. Descriptive Epidemiology Group of IARC (2008) GLOBOCAN 2002 database.
  3. 3.
    National Cancer Institute (2006) SEER Surveillance, Epidemiology and End Results: SEER Cancer Statistics Review, 1975–2003.
  4. 4.
    Abaid LN, Goldstein BH, Lopez KL, Micha JP, Brown JV, 3rd, Rettenmaier MA, Markman M (2010) The prognostic significance of optimal debulking in the setting of a complete clinical response for advanced ovarian carcinoma patients receiving maintenance chemotherapy. Arch Gynecol Obstet. doi: 10.1007/s00404-010-1571-5
  5. 5.
    Heintz AP, Odicino F, Maisonneuve P, Beller U, Benedet JL, Creasman WT, Ngan HY, Pecorelli S (2003) Carcinoma of the ovary. Int J Gynaecol Obstet 83(Suppl):1135–1166Google Scholar
  6. 6.
    Lenhard SM, Bufe A, Kumper C, Stieber P, Mayr D, Hertlein L, Kirschenhofer A, Friese K, Burges A (2009) Relapse and survival in early-stage ovarian cancer. Arch Gynecol Obstet 280(1):71–77. doi: 10.1007/s00404-008-0877-z PubMedCrossRefGoogle Scholar
  7. 7.
    Munstedt K, Hackethal A, Eskef K, Hrgovic I, Franke FE (2009) Prognostic relevance of granulocyte colony-stimulating factor in ovarian carcinomas. Arch Gynecol Obstet. doi: 10.1007/s00404-009-1319-2
  8. 8.
    Miyazawa M, Yasuda M, Fujita M, Hirasawa T, Kajiwara H, Hirabayashi K, Ogane N, Shimizu M, Asanuma H, Murakami M, Takekoshi S, Mikami M, Osamura RY (2009) Association of hypoxia-inducible factor-1 expression with histology in epithelial ovarian tumors: a quantitative analysis of HIF-1. Arch Gynecol Obstet 279(6):789–796. doi: 10.1007/s00404-008-0816-z PubMedCrossRefGoogle Scholar
  9. 9.
    Gungor T, Kanat-Pektas M, Sucak A, Mollamahmutoglu L (2009) The role of thrombocytosis in prognostic evaluation of epithelial ovarian tumors. Arch Gynecol Obstet 279(1):53–56. doi: 10.1007/s00404-008-0673-9 PubMedCrossRefGoogle Scholar
  10. 10.
    Hogdall EV, Christensen L, Kjaer SK, Blaakaer J, Kjaerbye-Thygesen A, Gayther S, Jacobs IJ, Hogdall CK (2007) CA125 expression pattern, prognosis and correlation with serum CA125 in ovarian tumor patients From The Danish “MALOVA” Ovarian Cancer Study. Gynecol Oncol 104(3):508–515PubMedCrossRefGoogle Scholar
  11. 11.
    Li J, Dowdy S, Tipton T, Podratz K, Lu WG, Xie X, Jiang SW (2009) HE4 as a biomarker for ovarian and endometrial cancer management. Expert Rev Mol Diagn 9(6):555–566. doi: 10.1586/erm.09.39 PubMedCrossRefGoogle Scholar
  12. 12.
    Zorn KK, Tian C, McGuire WP, Hoskins WJ, Markman M, Muggia FM, Rose PG, Ozols RF, Spriggs D, Armstrong DK (2009) The prognostic value of pretreatment CA 125 in patients with advanced ovarian carcinoma : a Gynecologic Oncology Group study. Cancer. doi: 10.1002/cncr.24084
  13. 13.
    Birchmeier W, Hulsken J, Behrens J ((1995)) E-cadherin as an invasion suppressor. Ciba Found Symp 189:124–136 (discussion 136–141, 174–126)Google Scholar
  14. 14.
    Birchmeier W, Behrens J (1994) Cadherin expression in carcinomas: role in the formation of cell junctions and the prevention of invasiveness. Biochim Biophys Acta 1198(1):11–26PubMedGoogle Scholar
  15. 15.
    Brinck U, Jacobs S, Neuss M, Tory K, Rath W, Kulle B, Fuzesi L (2004) Diffuse growth pattern affects E-cadherin expression in invasive breast cancer. Anticancer Res 24(4):2237–2242PubMedGoogle Scholar
  16. 16.
    Berx G, Van Roy F (2001) The E-cadherin–catenin complex: an important gatekeeper in breast cancer tumorigenesis and malignant progression. Breast Cancer Res 3(5):289–293PubMedCrossRefGoogle Scholar
  17. 17.
    Yalta T, Atay L, Atalay F, Caydere M, Gonultas M, Ustun H (2009) E-cadherin expression in endometrial malignancies: comparison between endometrioid and non-endometrioid carcinomas. J Int Med Res 37(1):163–168PubMedGoogle Scholar
  18. 18.
    Scholten AN, Aliredjo R, Creutzberg CL, Smit VT (2006) Combined E-cadherin, alpha-catenin, and beta-catenin expression is a favorable prognostic factor in endometrial carcinoma. Int J Gynecol Cancer 16(3):1379–1385PubMedCrossRefGoogle Scholar
  19. 19.
    Stawerski P, Wagrowska-Danilewicz M, Stasikowska O, Gottwald L, Danilewicz M (2008) Immunoexpression of beta-catenin–E-cadherin complex in primary serous ovarian tumors. Pol J Pathol 59(1):27–32PubMedGoogle Scholar
  20. 20.
    Blechschmidt K, Sassen S, Schmalfeldt B, Schuster T, Hofler H, Becker KF (2008) The E-cadherin repressor Snail is associated with lower overall survival of ovarian cancer patients. Br J Cancer 98(2):489–495. doi: 6604115[pii]10.1038/sj.bjc.6604115 PubMedCrossRefGoogle Scholar
  21. 21.
    Faleiro-Rodrigues C, Macedo-Pinto I, Pereira D, Lopes CS (2004) Prognostic value of E-cadherin immunoexpression in patients with primary ovarian carcinomas. Ann Oncol 15(10):1535–1542. doi: 10.1093/annonc/mdh38715/10/1535 PubMedCrossRefGoogle Scholar
  22. 22.
    Imai T, Horiuchi A, Shiozawa T, Osada R, Kikuchi N, Ohira S, Oka K, Konishi I (2004) Elevated expression of E-cadherin and alpha-, beta-, and gamma-catenins in metastatic lesions compared with primary epithelial ovarian carcinomas. Hum Pathol 35(12):1469–1476PubMedCrossRefGoogle Scholar
  23. 23.
    Marques FR, Fonsechi-Carvasan GA, De Angelo Andrade LA, Bottcher-Luiz F (2004) Immunohistochemical patterns for alpha- and beta-catenin, E- and N-cadherin expression in ovarian epithelial tumors. Gynecol Oncol 94(1):16–24PubMedCrossRefGoogle Scholar
  24. 24.
    Voutilainen KA, Anttila MA, Sillanpaa SM, Ropponen KM, Saarikoski SV, Juhola MT, Kosma VM (2006) Prognostic significance of E-cadherin–catenin complex in epithelial ovarian cancer. J Clin Pathol 59:460–467PubMedCrossRefGoogle Scholar
  25. 25.
    Yuecheng Y, Hongmei L, Xiaoyan X (2006) Clinical evaluation of E-cadherin expression and its regulation mechanism in epithelial ovarian cancer. Clin Exp Metastasis 23(1):65–74. doi: 10.1007/s10585-006-9020-3 PubMedCrossRefGoogle Scholar
  26. 26.
    Faleiro-Rodrigues C, Macedo-Pinto I, Pereira D, Ferreira VM, Lopes CS (2004) Association of E-cadherin and beta-catenin immunoexpression with clinicopathologic features in primary ovarian carcinomas. Hum Pathol 35(6):663–669PubMedCrossRefGoogle Scholar
  27. 27.
    Burges A, Bruning A, Dannenmann C, Blankenstein T, Jeschke U, Shabani N, Friese K, Mylonas I (2010) Prognostic significance of estrogen receptor alpha and beta expression in human serous carcinomas of the ovary. Arch Gynecol Obstet 281(3):511–517. doi: 10.1007/s00404-009-1185-y PubMedCrossRefGoogle Scholar
  28. 28.
    Dannenmann C, Shabani N, Friese K, Jeschke U, Mylonas I, Bruning A (2008) The metastasis-associated gene MTA1 is upregulated in advanced ovarian cancer, represses ERbeta, and enhances expression of oncogenic cytokine GRO. Cancer Biol Ther 7(9):1460–1467PubMedCrossRefGoogle Scholar
  29. 29.
    Anonymous (1989) FIGO stages (announcements)—revision. Gynecol Oncol 35 125–127Google Scholar
  30. 30.
    Mylonas I, Worbs S, Shabani N, Kuhn C, Kunze S, Schulze S, Dian D, Gingelmaier A, Schindlbeck C, Bruning A, Sommer H, Jeschke U, Friese K (2009) Inhibin-alpha subunit is an independent prognostic parameter in human endometrial carcinomas: analysis of inhibin/activin-alpha, -betaA and -betaB subunits in 302 cases. Eur J Cancer 45(7):1304–1314. doi: 10.1016/j.ejca.2009.01.008 PubMedCrossRefGoogle Scholar
  31. 31.
    Shabani N, Kuhn C, Kunze S, Schulze S, Mayr D, Dian D, Gingelmaier A, Schindlbeck C, Willgeroth F, Sommer H, Jeschke U, Friese K, Mylonas I (2007) Prognostic significance of oestrogen receptor alpha (ERalpha) and beta (ERbeta), progesterone receptor A (PR-A) and B (PR-B) in endometrial carcinomas. Eur J Cancer 43(16):2434–2444. doi: 10.1016/j.ejca.2007.08.014 PubMedCrossRefGoogle Scholar
  32. 32.
    Kaplan EL, Meier P (1958) Nonparametric estimation from incomplete observations. J Am Stat Assoc 53:457–481CrossRefGoogle Scholar
  33. 33.
    Perez-Moreno M, Jamora C, Fuchs E (2003) Sticky business: orchestrating cellular signals at adherens junctions. Cell 112:535–548PubMedCrossRefGoogle Scholar
  34. 34.
    Darai E, Scoazec JY, Walker-Combrouze F, Mlika-Cabanne N, Feldmann G, Madelenat P, Potet F (1997) Expression of cadherins in benign, borderline, and malignant ovarian epithelial tumors: a clinicopathologic study of 60 cases. Hum Pathol 28:922–928PubMedCrossRefGoogle Scholar
  35. 35.
    Fujioka T, Takebayashi Y, Kihana T, Kusanagi Y, Hamada K, Ochi H, Uchida T, Fukumoto M, Ito M (2001) Expression of E-cadherin and beta-catenin in primary and peritoneal metastatic ovarian carcinoma. Oncol Rep 8(2):249–255PubMedGoogle Scholar
  36. 36.
    Patel IS, Madan P, Getsios S, Bertrand MA, MacCalman CD (2003) Cadherin switching in ovarian cancer progression. Int J Cancer 106(2):172–177. doi: 10.1002/ijc.11086 PubMedCrossRefGoogle Scholar
  37. 37.
    Sundfeldt K, Piontkewitz Y, Ivarsson K, Nilsson O, Hellberg P, Brannstrom M, Janson PO, Enerback S, Hedin L (1997) E-cadherin expression in human epithelial ovarian cancer and normal ovary. Int J Cancer 74(3):275–280. doi: 10.1002/(SICI)1097-0215(19970620)74:3<275:AID-IJC7>3.0.CO;2-W PubMedCrossRefGoogle Scholar
  38. 38.
    Behrens J, Mareel MM, Van Roy FM, Birchmeier W (1989) Dissecting tumor cell invasion: epithelial cells acquire invasive properties after the loss of uvomorulin-mediated cell-cell adhesion. J Cell Biol 108(6):2435–2447PubMedCrossRefGoogle Scholar
  39. 39.
    Frixen UH, Behrens J, Sachs M, Eberle G, Voss B, Warda A, Lochner D, Birchmeier W (1991) E-cadherin-mediated cell-cell adhesion prevents invasiveness of human carcinoma cells. J Cell Biol 113(1):173–185PubMedCrossRefGoogle Scholar
  40. 40.
    Veatch AL, Carson LF, Ramakrishnan S (1994) Differential expression of the cell-cell adhesion molecule E-cadherin in ascites and solid human ovarian tumor cells. Int J Cancer 58(3):393–399PubMedCrossRefGoogle Scholar
  41. 41.
    Auersperg N, Pan J, Grove BD, Peterson T, Fisher J, Maines-Bandiera S, Somasiri A, Roskelley CD (1999) E-cadherin induces mesenchymal-to-epithelial transition in human ovarian surface epithelium. Proc Natl Acad Sci USA 96(11):6249–6254PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  1. 1.1st Department of Obstetrics and Gynecology, Campus InnenstadtLudwig-Maximilians-University MunichMunichGermany

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