Skip to main content

Advertisement

SpringerLink
Log in

Prognostic importance of survivin, Ki-67, and topoisomerase IIα in ovarian carcinoma

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

Abstract

Purpose

Stage, tumor grade and histological subtype determine the clinical behavior in ovarian tumors. Some additional factors are related to tumor cell biology and are the useful predictors for identifying the patients with poor prognosis. The aim of this study is to evaluate the prognostic significance of survivin, Ki-67 and Topoisomerase IIα (TOPO IIα) in epithelial ovarian cancer (EOC).

Materials and methods

Seventy-three patients with EOC were included in this study. Survivin, Ki-67 and TOPO IIα expressions were studied by immunohistochemistry on formalin-fixed, paraffin-embedded tissue sections. Nuclear staining for all antibodies was scored on a three-tiered system and more than 10 % staining was accepted as expression. The relationship between the expressions of survivin, Ki-67, TOPO IIα and clinicopathological parameters including age, stage, grade, platinum resistance and survival was evaluated.

Results

Survivin, Ki-67 and TOPO IIα expressions were found in 20, 82 and 86 % of the tumors, respectively. Ki-67 and TOPO IIα expressions were found to be related to poor overall survival (p = 0.005, 0.004, respectively), while survivin expression was not associated with overall survival. There was no association between TOPO IIα and Ki-67 expressions and histological subtype, stage or grade. However, we found an important relationship between TOPO IIα expression and platinum resistance (p = 0.044). Platinum resistance was found to be an independent prognostic factor in EOC.

Conclusion

Ki-67 and TOPO IIα expressions were found to be related to poor overall survival, and TOPO IIα expression was found to be associated with platinum resistance.

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. Thompson CB (1995) Apoptosis in the pathogenesis and treatment of disease. Science 267:1456–1462

    Article  CAS  PubMed  Google Scholar 

  2. Hickman JA (1992) Apoptosis induced by anticancer drugs. Cancer Metast Rev 11:121–139

    Article  CAS  Google Scholar 

  3. Salvesen GS, Duckett CS (2002) Apoptosis : IAP proteins: blocking the road to death’s door. Nat Rev Mol Cell Biol 3:401–410

    Article  CAS  PubMed  Google Scholar 

  4. Li F (2003) Survivin study: what is the next wave? J Cell Physiol 197:8–29

    Article  CAS  PubMed  Google Scholar 

  5. Ambrosini G, Adida C, Altieri DC (1997) A novel anti-apoptosis gene, survivin, expressed in cancer and lymphoma. Nat Med 3:917–921

    Article  CAS  PubMed  Google Scholar 

  6. Ueda M, Yamashita Y, Takehara M, Terai Y, Kumagai K, Ueki K, Kanda K, Yamaguchi H, Akise D, Hung YC, Ueki M (2002) Survivin gene expression in endometriosis. J Clin Endocrinol Metab 87(7):3452–3459

    CAS  PubMed  Google Scholar 

  7. Kanno R, Yamakava H, Utsunomiya H, Ito K, Sato S, Yajima A (2006) Expression of survivin and Bcl-2 in the normal endometrium. Mol Human Repr 6:529–534

    Article  Google Scholar 

  8. Zaffaroni N, Pennati M, Colella G, Perego P, Supino R, Gatti L, Pilotti S, Zunino F, Daidone MG (2002) Expression of the anti-apoptotic gene survivin correlates with taxol resistance in human ovarian cancer. Cell Mol Life Sci 59:1406–1412

    Article  CAS  PubMed  Google Scholar 

  9. Cattoretti G, Becker MH, Key G, Duchrow M, Schluter C, Galle J, Gerdes J (1992) Monoclonal antibodies against recombinant parts of the Ki- 67 antigen (MIB 1 and MIB 3) detect proliferating cells in microwave-processed formalinfixed paraffin sections. J Pathol 168:357–363

    Article  CAS  PubMed  Google Scholar 

  10. Wang JC (2002) Cellular roles of DNA topoisomerases: a molecular perspective. Nat Rev Mol Cell Biol 3:430–440

    Article  CAS  PubMed  Google Scholar 

  11. Gotlieb WH, Goldberg I, Weisz B, Davidson B, Novikov I, Kopolovic J, Ben- Baruch G (2001) Topoisomerase II immunostaining as prognostic marker for survival in ovarian cancer. Gynecol Oncol 82:99–104

    Article  CAS  PubMed  Google Scholar 

  12. Brustmann H (2004) Vascular endothelial growth factor expression in serous ovarian carcinoma: relationship with topoisomerase IIα and prognosis. Gynecol Oncol 95:16–22

    Article  CAS  PubMed  Google Scholar 

  13. Ferrandina G, Petrillo M, Carbone A, Zannoni G, Martinelli E, Prisco M, Pignata S, Breda E, Savarese A, Scambia G (2008) Prognostic role of topoisomerase-IIα in advanced ovarian cancer patients. Br J Cancer 98:1910–1915

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  14. Benedet JL, Bender H, Jones H, Ngan HY, Pecorelli S (2000) FIGO staging classifications and clinical practice guidelines in the management of gynecologic cancers FIGO Committee on gynecologic oncology. Int J Gynecol Obstet 70:209–262

    Article  CAS  Google Scholar 

  15. Ferrandina G, Legge F, Martinelli E, Ranelletti FO, Zannoni GF, Lauriola L, Gessi M, Gallotta V, Scambia G (2005) Survivin expression in ovarian cancer and its correlation with clinico-pathological, surgical and apoptosis-related parameters. Br J Cancer 92:271–277

    CAS  PubMed Central  PubMed  Google Scholar 

  16. Li F, Yang J, Ramnath N, Javle MM, Tan D (2005) Nuclear or cytoplasmic expression of survivin: what is the significance? Int J Cancer 114(4):509–512

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  17. Kleinberg L, Florenes VA, Silins I, Haug K, Trope CG, Nesland JM, Davidson B (2007) Nuclear expression of survivin is associated with improved survival in metastatic ovarian carcinoma. Cancer 109:228–238

    Article  CAS  PubMed  Google Scholar 

  18. Cohen C, Lohmann CM, Cotsonis G, Lawson D, Santoianni R (2003) Survivin expression in ovarian carcinoma: correlation with apoptotic markers and prognosis. Mod Pathol 16(6):574–583

    Article  PubMed  Google Scholar 

  19. Kar R, Sen S, Singh A, Sharma H, Kumar S, Gupta SD, Singh N (2007) Role of apoptotic regulators in human epithelial ovarian cancer. Cancer Biol Ther 6(7):1101–1105

    Article  CAS  PubMed  Google Scholar 

  20. Yoshida H, Ishiko O, Sumi T, Matsumoto Y, Ogita S (2001) Survivin, bcl-2 and matrix metalloproteinase-2 enhance progression of clear cell- and serous-type ovarian carcinomas. Int J Oncol 19:537–542

    CAS  PubMed  Google Scholar 

  21. Sui L, Dong Y, Ohno M, Watanabe Y, Sugimoto K, Tokuda M (2002) Survivin expression and its correlation with cell proliferation and prognosis in epithelial ovarian tumors. Int J Oncol 21:315–320

    CAS  PubMed  Google Scholar 

  22. Mita S, Nakai A, Maeda S, Takeshita T (2004) Prognostic significance of Ki-67 antigen immunostaining (MIB-1 monoclonal antibody) in ovarian cancer. J Nippon Med Sch 71(6):384–391

    Article  CAS  PubMed  Google Scholar 

  23. Kommoss S, du Bois A, Schmidt D, Parwaresch R, Pfisterer J, Kommoss F (2006) Chemotherapy may be more effective in highly proliferative ovarian carcinomas–a translational research subprotocol of a prospective randomized phase III study (AGO-OVAR 3 protocol). Gynecol Oncol 103:67–71

    Article  CAS  PubMed  Google Scholar 

  24. Bristow RE, Tomacruz RS, Armstrong DK, Trimble EL, Montz FJ (2002) Survival effect of maximal cytoreductive surgery for advanced ovarian carcinoma during the platinum Era: a meta-analysis. J Clin Oncol 20(5):1248–1259

    Article  PubMed  Google Scholar 

  25. Chekerov R, Klaman I, Zafrakas M, Konsgen D, Mustea A, Petschke B, Lightenegger J, Dahl E (2006) Altered expression pattern of Topoisomerase IIα in ovarian tumor epithelial and stromal cells after platinum based chemotherapy. Neoplasia 8(1):38–45

    Article  CAS  PubMed Central  PubMed  Google Scholar 

Download references

Conflict and interest

None.

Author information

Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Faculty of Medicine, Cukurova University, 01330, Adana, Turkey

    Umran Kucukgoz Gulec, Ahmet Baris Guzel, Ghanim Khatib, Mehmet Ali Vardar & Aytekin Altintas

  2. Department of Pathology, Faculty of Medicine, Cukurova University, Adana, Turkey

    Derya Gumurdulu, Arbil Acikalin & Handan Zeren

  3. Department of Medical Oncology, Faculty of Medicine, Cukurova University, Adana, Turkey

    Semra Paydas

  4. Department of Biostatistics, Faculty of Medicine, Cukurova University, Adana, Turkey

    Gulsah Seydaoglu

Authors
  1. Umran Kucukgoz Gulec
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Derya Gumurdulu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ahmet Baris Guzel
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Semra Paydas
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Gulsah Seydaoglu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Arbil Acikalin
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ghanim Khatib
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Handan Zeren
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Mehmet Ali Vardar
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Aytekin Altintas
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Umran Kucukgoz Gulec.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kucukgoz Gulec, U., Gumurdulu, D., Guzel, A.B. et al. Prognostic importance of survivin, Ki-67, and topoisomerase IIα in ovarian carcinoma. Arch Gynecol Obstet 289, 393–398 (2014). https://doi.org/10.1007/s00404-013-3000-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00404-013-3000-z

Keywords

Search

Navigation