Skip to main content
SpringerLink
Log in

Overexpression of Aurora B is associated with poor prognosis in epithelial ovarian cancer patients

  • Original Article
  • Published:
Virchows Archiv Aims and scope Submit manuscript

Abstract

Recent studies have indicated that Aurora B expression is related to cell proliferation and prognosis in many cancers, but its association with epithelial ovarian carcinoma is not fully understood. Therefore, we examined the Aurora B kinase expression in epithelial ovarian cancer patients. Using immunohistochemistry, the expression levels of Aurora B and phosphohistone H3 (Ser10) (mitosis-specific marker) were measured in 156 patients with epithelial ovarian cancer. The expression levels of Aurora B at the protein and messenger RNA levels were examined using Western blotting and reverse transcriptase polymerase chain reaction. In total, 53 tumorous ovarian samples (34.0%) showed Aurora B overexpression, which was significantly higher than that found in the 15 normal ovarian tissue samples (0%, p = 0.006). The overexpression of Aurora B was also significantly higher in cases showing phosphohistone H3 (Ser10) overexpression (44.3% vs. 27.4%, p = 0.03). In addition, the expression of Aurora B in poorly and moderately differentiated carcinomas of the ovary was significantly higher than in well-differentiated carcinomas (53.6% vs. 28.2% vs.10.0%, respectively, p = 0.02). The overexpression of Aurora B was significantly higher in cases with lymph node metastasis (p = 0.01) and a positive ascites cytology (p = 0.008). Overall, the Aurora B overexpression group demonstrated a significantly shorter progression-free survival (p = 0.001) and overall survival (p = 0.023) than the Aurora B low expression group using univariate analysis (log-rank statistic). Aurora B is an effective predictor of aggressive epithelial ovarian carcinoma in terms of differentiation, metastasis, and prognosis.

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
Fig. 3

Similar content being viewed by others

References

  1. NCI Surveillance, E.a.E.R.S.P.a.t.N.C.f.H.S. National Cancer Institute—a snapshot of ovarian cancer: incidence and mortality rate trends 2006 Sep. http://planning.cancer.gov/disease/ovarian-snapshot.pdf

  2. Hoskins WJ, Perez CA, Young RC (2000) Principles and practice of gynecologic oncology. Lippincott Williams and Wilkins, Philadelphia, pp 1005–1007

    Google Scholar 

  3. Adams RR, Carmena M, Earnshaw WC (2001) Chromosomal passengers and the (Aurora) ABCs of mitosis. Trends Cell Biol 11:49–54

    Article  CAS  PubMed  Google Scholar 

  4. Tatsuka M, Katayama H, Ota T et al (1998) Multinuclearity and increased ploidy caused by overexpression of the aurora- and Ipl1-like midbody-associated protein mitotic kinase in human cancer cells. Cancer Res 58:4811–4816

    CAS  PubMed  Google Scholar 

  5. Kaitna S, Pasierbek P, Jantsch M et al (2002) The aurora B kinase AIR-2 regulates kinetochores during mitosis and is required for separation of homologous chromosomes during meiosis. Curr Biol 12:798–812

    Article  CAS  PubMed  Google Scholar 

  6. Ota T, Suto S, Katayama H et al (2002) Increased mitotic phosphorylation of histone H3 attributable to AIM-1/Aurora-B overexpression contributes to chromosome number instability. Cancer Res 62:5168–5177

    CAS  PubMed  Google Scholar 

  7. Murata-Hori M, Wang YL (2002) Both midzone and astral microtubules are involved in the delivery of cytokinesis signals: insights from the mobility of aurora B. J Cell Biol 159:45–53

    Article  CAS  PubMed  Google Scholar 

  8. Sorrentino R, Libertini S, Pallante PL et al (2005) Aurora B overexpression associates with the thyroid carcinoma undifferentiated phenotype and is required for thyroid carcinoma cell proliferation. J Clin Endocrinol Metab 90:928–935

    Article  CAS  PubMed  Google Scholar 

  9. Katayama H, Ota T, Jisaki F et al (1999) Mitotic kinase expression and colorectal cancer progression. J Natl Cancer Inst 91:1160–1162

    Article  CAS  PubMed  Google Scholar 

  10. Sistayanarain A, Tsuneyama K, Zheng H et al (2006) Expression of Aurora-B kinase and phosphorylated histone H3 in hepatocellular carcinoma. Anticancer Res 26:3585–3593

    CAS  PubMed  Google Scholar 

  11. Ulisse S, Delcros JG, Baldini E et al (2006) Expression of Aurora kinases in human thyroid carcinoma cell lines and tissues. Int J Cancer 119:275–282

    Article  CAS  PubMed  Google Scholar 

  12. Hayama S, Daigo Y, Yamabuki T et al (2007) Phosphorylation and activation of cell division cycle associated 8 by aurora kinase B plays a significant role in human lung carcinogenesis. Cancer Res 67:4113–4122

    Article  CAS  PubMed  Google Scholar 

  13. Remmele W, Schicketanz KH (1993) Immunohistochemical determination of estrogen and progesterone receptor content in human breast cancer. Computer-assisted image analysis (QIC score) vs subjective grading (IRS). Pathol Res Pract 8:227–245

    Google Scholar 

  14. Chieffi P, Cozzolino L, Kisslinger A et al (2006) Aurora B expression directly correlates with prostate cancer malignancy and influence prostate cell proliferation. Prostate 66:326–333

    Article  CAS  PubMed  Google Scholar 

  15. Kurai M, Shiozawa T, Shih HC et al (2005) Expression of Aurora kinases A and B in normal, hyperplastic and malignant human endometrium: Aurora B as a predictor for poor prognosis in endometrial carcinoma. Hum Pathol 36:1281–1288

    Article  CAS  PubMed  Google Scholar 

  16. Kulkarni AA, Loddo M, Leo E et al (2007) DNA replication licensing factors and aurora kinases are linked to aneuploidy and clinical outcome in epithelial ovarian carcinoma. Clin Cancer Res 13:6153–6161

    Article  CAS  PubMed  Google Scholar 

  17. Hendzel MJ, Wei Y, Mancini MA et al (1997) Mitosis-specific phosphorylation of histone H3 initiates primarily within pericentromeric heterochromatin during G2 and spreads in an ordered fashion coincident with mitotic chromosome condensation. Chromosoma 106:348–360

    Article  CAS  PubMed  Google Scholar 

  18. Kim YJ, Ketter R, Steudel WI et al (2007) Prognostic significance of the mitotic index using the mitosis marker anti-phosphohistone H3 in meningiomas. Am J Clin Pathol 128:118–125

    Article  CAS  PubMed  Google Scholar 

  19. Rosai J (2004) Ackerman’s surgical pathology, 9th edn. Mosby, St. Louis

    Google Scholar 

  20. Köbel M, Kalloger SE, Boyd N et al (2008) Ovarian carcinoma subtypes are different diseases: implications for biomarker studies. PLoS Med 5:e232

    Article  PubMed  Google Scholar 

  21. Soslow RA (2008) Histologic subtypes of ovarian carcinoma: an overview. Int J Gynecol Pathol 27:161–174

    PubMed  Google Scholar 

  22. Lee EC, Frolov A, Li R et al (2006) Targeting Aurora kinases for the treatment of prostate cancer. Cancer Res 66:4996–5002

    Article  CAS  PubMed  Google Scholar 

  23. Remmele W, Schicketanz KH (1993) Immunohistochemical determination of estrogen and progesterone receptor content in human breast cancer. Computer-assisted image analysis (QIC score) vs. subjective grading (IRS). Pathol Res Pract 189:862–866

    CAS  PubMed  Google Scholar 

  24. Twu NF, Yuan CC, Yen MS et al (2009) Expression of aurora kinase A and B in normal and malignant cervical tissue: high Aurora A kinase expression in squamous cervical cancer. Eur J Obstet Gynecol Reprod Biol 142:57–63

    Article  CAS  PubMed  Google Scholar 

  25. Chen CM, Behringer RR (2004) Ovca1 regulates cell proliferation, embryonic development, and tumorigenesis. Genes Dev 18:320–332

    Article  CAS  PubMed  Google Scholar 

  26. Kaplan E, Meyer P (1958) Non parametric estimation from incomplete observations. J Am Stat Assoc 53:457–481

    Article  Google Scholar 

  27. Altman DG, Lausen B, Sauerbrei W et al (1994) Dangers of using “Optimal” cut points in the evaluation of prognostic factors. J Natl Cancer Inst 86:829–835

    Article  CAS  PubMed  Google Scholar 

  28. Cox DR (1970) Analysis of binary data. Methuen, London

    Google Scholar 

  29. Andrews PD, Knatko E, Moore WJ et al (2003) Mitotic mechanics: the Auroras come into view. Curr Opin Cell Biol 15:672–683

    Article  CAS  PubMed  Google Scholar 

  30. Ruchaud S, Carmena M, Earnshaw WC (2007) The chromosomal passenger complex: one for all and all for one. Cell 131:230–231

    Article  CAS  PubMed  Google Scholar 

  31. Hsu JY, Sun ZW, Li X et al (2000) Mitotic phosphorylation of histone H3 is governed by Ipl1/aurora kinase and Glc7/PP1 phosphatase in budding yeast and nematodes. Cell 102:279–291

    Article  CAS  PubMed  Google Scholar 

  32. Hendzel MJ, Wei Y, Mancini MA et al (1997) Mitosis-specific phosphorylation of histone H3 initiates primarily within pericentromeric heterochromatin during G2 and spreads in an ordered fashion coincident with mitotic chromosome condensation. Chromosoma 106:348–360

    Article  CAS  PubMed  Google Scholar 

  33. Wei Y, Yu L, Bowen J et al (1999) Phosphorylation of histone H3 is required for proper chromosome condensation and segregation. Cell 97:99–109

    Article  CAS  PubMed  Google Scholar 

  34. Wheatley SP, Barrett RM, Andrews PD et al (2007) Phosphorylation by aurora-B negatively regulates survivin function during mitosis. Cell Cycle 6:1220–1230

    CAS  PubMed  Google Scholar 

  35. Jacobberger JW, Frisa PS, Sramkoski RM et al (2008) A new biomarker for mitotic cells. Cytometry A 73:5–15

    PubMed  Google Scholar 

  36. Kim YJ, Ketter R, Steudel WI et al (2007) Prognostic significance of the mitotic index using the mitosis marker anti-phosphohistone H3 in meningiomas. Am J Clin Pathol 128:118–125

    Article  CAS  PubMed  Google Scholar 

  37. Qi G, Ogawa I, Kudo Y et al (2007) Aurora-B expression and its correlation with cell proliferation and metastasis in oral cancer. Virchows Arch 450:297–302

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We thank Ching-Fen Yang for her evaluation of the immunohistochemical score. We appreciate Professor Ralphy Kirby’s help in improving the style of written English. We thank Dr. Muh-Hwa Yang for his involvement in revising the manuscript. We are grateful for the assistance of Miss Tsui-Ying Huang in completing the RT-PCR and Western blots. This research was supported, in part, by grant 96-VGH-B1-010 from Veterans General Hospital and by a grant from the Ministry of Education “Aim for the Top University” Plan. This study was also supported by research grants from Yen-Tjing-Ling Medical Foundation (CI-97-6).

Conflict of interest statement

We declare that we have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei, Taiwan

    Yi-Jen Chen, Nae-Fang Twu, Ming-Shyen Yen, Hua-Hsi Wu, Peng-Hui Wang & Chiou-Chung Yuan

  2. Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan

    Yi-Jen Chen, Hua-Hsi Wu, Peng-Hui Wang & Chiou-Chung Yuan

  3. Department of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taipei, Taiwan

    Chun-Ming Chen, Nae-Fang Twu & Ming-Shyen Yen

  4. Department of Pathology, Taipei Veterans General Hospital, Taipei, Taiwan

    Chiung-Ru Lai

  5. Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, 201, Section 2, Shih-Pai Road, Taipei, 112, Taiwan

    Chiou-Chung Yuan

Authors
  1. Yi-Jen Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chun-Ming Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nae-Fang Twu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ming-Shyen Yen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Chiung-Ru Lai
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hua-Hsi Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Peng-Hui Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Chiou-Chung Yuan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Chiou-Chung Yuan.

Additional information

Authors’ contributions

Yi-Jen Chen carried out immunohistochemical staining, performed the statistical analysis, and drafted the manuscript. Chun-Ming Chen carried out the RT-PCR, Western blot and drafted the manuscript. Chiung-Ru Lai assessed the pathological specimens and evaluated the immunohistochemical score. Nae-Fang Twu, Ming-Shyen Yen, Hua-Hsi Wu, and Peng-Hui Wang participated in the design of the study and provided patients’ data. Chiou-Chung Yuan conceived of the study and participated in its design and coordination. All authors read and approved the final manuscript.

C.-M. Chen and C.-C. Yuan contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chen, YJ., Chen, CM., Twu, NF. et al. Overexpression of Aurora B is associated with poor prognosis in epithelial ovarian cancer patients. Virchows Arch 455, 431–440 (2009). https://doi.org/10.1007/s00428-009-0838-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00428-009-0838-3

Keywords

Search

Navigation