Skip to main content
SpringerLink
Log in

Prognostic role of E-cadherin in patients with advanced serous ovarian cancer

  • Gynecologic Oncology
  • Published:
Archives of Gynecology and Obstetrics Aims and scope Submit manuscript

Abstract

Purpose

To analyse correlation between expression of E-cadherin and clinical and pathological features and overall survival in advanced-stage serous ovarian carcinoma.

Methods

The expression of E-cadherin was analysed immunohistochemically in formalin-fixed, paraffin-embedded samples from 54 patients with advanced-stage serous ovarian cancer and related to clinicopathological characteristics and patients survival. The clinicopathological characteristics included the stage according to the International Federation of Gynecology and Obstetrics (FIGO), tumour differentiation, number of mitoses per 10 high-power fields (HPF), residual tumour size, and vascular invasion. Only patients with serous ovarian cancer FIGO stages III–IV were included. Overall survival (OS) was defined as time from surgery to the last follow-up date on 01.10.2010. OS was evaluated using Kaplan–Meier method, and log-rank test was used to asses the differences between the positive and E-cadherin negative group. Multivariate analysis was completed using the Cox proportional hazard regression model.

Results

E-cadherin immunoreactivity was not associated with FIGO stage, tumour grade, number of mitotic figures per 10 HPF, residual tumour volume or vascular invasion. Negative E-cadherin expression significantly predicted shorter OS (p < 0.001). The multivariate analyses showed that negative E-cadherin (p < 0.001), FIGO stage (p = 0.012) and residual tumour size >1 cm after the initial cytoreductive surgery (p < 0.001) were predictors of shorter OS.

Conclusion

Negative E-cadherin expression like presence of residual tumour after primary cytoreductive surgery and higher FIGO stage seem to predict unfavourable clinical outcome in patients with advanced-stage serous ovarian cancer. Negative expression of E-cadherin was shown to be a significant independent predictor of poorer OS. E-cadherin as marker has prognostic value.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Ozols RF, Rubin SC, Thomas GM, Robboy SJ (2000) Epithelial ovarian cancer. In: Principles and practice of gynecologic oncology, 3rd edn. Lippincott, Williams and Wilkins, Philadelphia, pp 895–896

  2. Seidman JD, Kurman RJ (2003) Pathology of ovarian carcinoma. Hematol Oncol Clin North Am 17(4):909–925 vii

    Article  PubMed  Google Scholar 

  3. Jemal A, Murray T, Ward E, Samuels A, Tiwari RC, Ghafoor A, Feuer EJ, Thun MJ (2005) Cancer statistics, 2005. CA Cancer J Clin 55(1):10–30

    Article  PubMed  Google Scholar 

  4. Shimamura T, Une Y, Nakajima Y, Sato N, Matsushita M, Kamiyama T, Haneda T, Nakanishi K, Akabane H, Tomioka N et al (1995) Advantages and disadvantages of the intraarterial chemotherapy using a reservoir as postoperative adjuvant therapy for hepatocellular carcinoma. Gan To kagaku Ryoho Cancer Chemother 22(11):1511–1514

    CAS  Google Scholar 

  5. Putzke AP, Ventura AP, Bailey AM, Akture C, Opoku-Ansah J, Celiktas M, Hwang MS, Darling DS, Coleman IM, Nelson PS, Nguyen HM, Corey E, Tewari M, Morrissey C, Vessella RL, Knudsen BS (2011) Metastatic progression of prostate cancer and e-cadherin regulation by zeb1 and SRC family kinases. Am J Pathol 179(1):400–410. doi:10.1016/j.ajpath.2011.03.028

    Article  PubMed  CAS  Google Scholar 

  6. Luber B, Deplazes J, Keller G, Walch A, Rauser S, Eichmann M, Langer R, Hofler H, Hegewisch-Becker S, Folprecht G, Woll E, Decker T, Endlicher E, Lorenzen S, Fend F, Peschel C, Lordick F (2011) Biomarker analysis of cetuximab plus oxaliplatin/leucovorin/5-fluorouracil in first-line metastatic gastric and oesophago-gastric junction cancer: results from a phase II trial of the Arbeitsgemeinschaft Internistische Onkologie (AIO). BMC Cancer 11:509. doi:10.1186/1471-2407-11-509

    Article  PubMed  CAS  Google Scholar 

  7. Wimberger P, Wehling M, Lehmann N, Kimmig R, Schmalfeldt B, Burges A, Harter P, Pfisterer J, du Bois A (2010) Influence of residual tumor on outcome in ovarian cancer patients with FIGO stage IV disease: an exploratory analysis of the AGO-OVAR (Arbeitsgemeinschaft Gynaekologische Onkologie Ovarian Cancer Study Group). Ann Surg Oncol 17(6):1642–1648. doi:10.1245/s10434-010-0964-9

    Article  PubMed  Google Scholar 

  8. Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J (2009) New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 45(2):228–247. doi:10.1016/j.ejca.2008.10.026

    Article  PubMed  CAS  Google Scholar 

  9. Malpica A, Deavers MT, Lu K, Bodurka DC, Atkinson EN, Gershenson DM, Silva EG (2004) Grading ovarian serous carcinoma using a two-tier system. Am J Surg Pathol 28(4):496–504

    Article  PubMed  Google Scholar 

  10. Bodurka DC, Deavers MT, Tian C, Sun CC, Malpica A, Coleman RL, Lu KH, Sood AK, Birrer MJ, Ozols R, Baergen R, Emerson RE, Steinhoff M, Behmaram B, Rasty G, Gershenson DM (2012) Reclassification of serous ovarian carcinoma by a 2-tier system: a gynecologic oncology group study. Cancer 118(12):3087–3094. doi:10.1002/cncr.26618

    Article  PubMed  Google Scholar 

  11. 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 1):135–166

    Article  PubMed  Google Scholar 

  12. Shimizu Y, Kamoi S, Amada S, Akiyama F, Silverberg SG (1998) Toward the development of a universal grading system for ovarian epithelial carcinoma: testing of a proposed system in a series of 461 patients with uniform treatment and follow-up. Cancer 82(5):893–901

    Article  PubMed  CAS  Google Scholar 

  13. Peng HL, He L, Zhao X (2012) Association of reduced immunohistochemical expression of E-cadherin with a poor ovarian cancer prognosis—results of a meta-analysis. Asian Pac J Cancer Prev 13(5):2003–2007

    Article  PubMed  Google Scholar 

  14. Ho CM, Cheng WF, Lin MC, Chen TC, Huang SH, Liu FS, Chien CC, Yu MH, Wang TY, Hsieh CY (2010) Prognostic and predictive values of E-cadherin for patients of ovarian clear cell adenocarcinoma. Int J Gynecol Cancer 20(9):1490–1497. doi:10.1111/IGC.0b013e3181e68a4d

    PubMed  Google Scholar 

  15. 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/mdh387

    Article  PubMed  CAS  Google Scholar 

  16. 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(8):922–928

    Article  PubMed  CAS  Google Scholar 

  17. Cho EY, Choi Y, Chae SW, Sohn JH, Ahn GH (2006) Immunohistochemical study of the expression of adhesion molecules in ovarian serous neoplasms. Pathol Int 56(2):62–70. doi:10.1111/j.1440-1827.2006.01925.x

    Article  PubMed  CAS  Google Scholar 

  18. 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:10.1038/sj.bjc.6604115

    Article  PubMed  CAS  Google Scholar 

  19. Koensgen D, Freitag C, Klaman I, Dahl E, Mustea A, Chekerov R, Braicu I, Lichtenegger W, Sehouli J (2010) Expression and localization of e-cadherin in epithelial ovarian cancer. Anticancer Res 30(7):2525–2530

    PubMed  CAS  Google Scholar 

  20. 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(5):460–467. doi:10.1136/jcp.2005.029876

    Article  PubMed  CAS  Google Scholar 

  21. Shim HS, Yoon BS, Cho NH (2009) Prognostic significance of paired epithelial cell adhesion molecule and E-cadherin in ovarian serous carcinoma. Hum Pathol 40(5):693–698. doi:10.1016/j.humpath.2008.10.013

    Article  PubMed  CAS  Google Scholar 

  22. Dian D, Bruning A, Mylonas I (2011) E-cadherin as a prognostic marker in human serous carcinomas of the ovary: an immunohistochemical analysis. Arch Gynecol Obstet 284(2):437–443. doi:10.1007/s00404-010-1657-0

    Article  PubMed  CAS  Google Scholar 

  23. Davidson B, Gotlieb WH, Ben-Baruch G, Nesland JM, Bryne M, Goldberg I, Kopolovic J, Berner A (2000) E-Cadherin complex protein expression and survival in ovarian carcinoma. Gynecol Oncol 79(3):362–371. doi:10.1006/gyno.2000.5964

    Article  PubMed  CAS  Google Scholar 

  24. Landen CN Jr, Birrer MJ, Sood AK (2008) Early events in the pathogenesis of epithelial ovarian cancer. J Clin Oncol 26(6):995–1005. doi:10.1200/JCO.2006.07.9970

    Article  PubMed  Google Scholar 

  25. Davies BR, Worsley SD, Ponder BA (1998) Expression of E-cadherin, alpha-catenin and beta-catenin in normal ovarian surface epithelium and epithelial ovarian cancers. Histopathology 32(1):69–80

    Article  PubMed  CAS  Google Scholar 

  26. 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. Human Pathol 35(12):1469–1476

    Article  CAS  Google Scholar 

  27. Hudson LG, Zeineldin R, Stack MS (2008) Phenotypic plasticity of neoplastic ovarian epithelium: unique cadherin profiles in tumor progression. Clin Exp Met 25(6):643–655. doi:10.1007/s10585-008-9171-5

    Article  CAS  Google Scholar 

  28. Cheung LW, Leung PC, Wong AS (2010) Cadherin switching and activation of p120 catenin signaling are mediators of gonadotropin-releasing hormone to promote tumor cell migration and invasion in ovarian cancer. Oncogene 29(16):2427–2440. doi:10.1038/onc.2009.523

    Article  PubMed  CAS  Google Scholar 

  29. Sivertsen S, Berner A, Michael CW, Bedrossian C, Davidson B (2006) Cadherin expression in ovarian carcinoma and malignant mesothelioma cell effusions. Acta Cytol 50(6):603–607

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported in part by a Grant No: 216-0000000-0484 from the Ministry of Science, Education and sports of the Republic of Croatia.

Conflict of interest

None.

Author information

Authors and Affiliations

  1. Department of Obstetrics and Gynaecology, Split University Hospital Centre and School of Medicine, Spinčićeva 1, 21000, Split, Croatia

    Boris Bačić

  2. Department of Obstetrics and Gynaecology, Rijeka University Hospital Centre and School of Medicine, Rijeka, Croatia

    Herman Haller

  3. Department of Pathology, Split University Hospital Centre and School of Medicine, Split, Croatia

    Ivana Mrklić & Snježana Tomić

  4. Department of Anatomy, Split University School of Medicine, Split, Croatia

    Vana Košta & Ana Čarić

Authors
  1. Boris Bačić
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Herman Haller
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ivana Mrklić
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Vana Košta
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ana Čarić
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Snježana Tomić
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Boris Bačić.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bačić, B., Haller, H., Mrklić, I. et al. Prognostic role of E-cadherin in patients with advanced serous ovarian cancer. Arch Gynecol Obstet 287, 1219–1224 (2013). https://doi.org/10.1007/s00404-012-2684-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00404-012-2684-9

Keywords

Search

Navigation