Tumor Biology

, Volume 36, Issue 2, pp 953–957 | Cite as

Prognostic value of cyclin B in endometrial endometrioid adenocarcinoma

  • Simi Santala
  • Anne Talvensaari-Mattila
  • Ylermi Soini
  • Markku Santala
Research Article


Cyclins are a group of cell cycle regulatory proteins. Cyclin B acts as an activator to cyclin-dependent kinase 1 (CDK1), a protein kinase essential for G2/M phase transition. Deregulation of cyclins has been linked to a number of malignant neoplasms, but the impact on clinicopathological parameters seems to be cancer-specific. Overexpression of cyclin B has been shown to affect survival in some malignant tumors, including breast and esophageal cancer, but its impact on endometrial cancer has not been extensively studied. For this study, 211 endometrial endometrioid adenocarcinoma samples were obtained from patients surgically treated at the Oulu University Hospital. The samples were immunohistochemically stained and analyzed for cyclin B expression. The relationships between cyclin B expression and conventional prognostic factors were analyzed. A discrimination threshold for survival analyses was calculated by utilizing the receiver operator characteristic (ROC) method. Cyclin B expression correlated with grade and advanced stage. Survival analyses showed that cyclin B expression affects cancer-specific survival in univariate analysis. In multivariate analysis, the results were indicative that cyclin B may hold independent prognostic significance, but further studies are required to assess this.


Cyclin B CDKs Endometrial adenocarcinoma Prognosis 


Conflicts of interest



  1. 1.
    Finnish Cancer Registry. Cancer Statistics. 2012. Accessed: 9 May 2014.
  2. 2.
    Creasman WT, Odicino F, Maisonneuve P, Quinn MA, Beller U, et al. Carcinoma of the corpus uteri. FIGO 26th annual report on the results of treatment in gynecological cancer. Int J Gynecol Obstet. 2006;95 Suppl 1:S105–43.CrossRefGoogle Scholar
  3. 3.
    Creasman W. Revised FIGO staging for carcinoma of the endometrium. Int J Gynecol Obstet. 2009;105(2):109.CrossRefGoogle Scholar
  4. 4.
    Gadducci A, Cosio S, Genazzani AR. Tissue and serum biomarkers as prognostic variables in endometrioid-type endometrial cancer. Crit Rev Oncol Hematol. 2011;80(2):181–92.CrossRefPubMedGoogle Scholar
  5. 5.
    Harashima H, Dissmeyer N, Schnittger A. Cell cycle control across the eukaryotic kingdom. Trends Cell Biol. 2013;23(7):345–56.CrossRefPubMedGoogle Scholar
  6. 6.
    Malumbres M, Barbacid M. Cell cycle, CDKs and cancer: a changing paradigm. Nat Rev Cancer. 2009;9(3):153–66.CrossRefPubMedGoogle Scholar
  7. 7.
    Doree M, Hunt T. From Cdc2 to Cdk1: When did the cell cycle kinase join its cyclin partner? J Cell Sci. 2002;115(Pt 12):2461–4.PubMedGoogle Scholar
  8. 8.
    Singhal S, Vachani A, Antin-Ozerkis D, Kaiser LR, Albelda SM. Prognostic implications of cell cycle, apoptosis, and angiogenesis biomarkers in non-small cell lung cancer: a review. Clin Cancer Res. 2005;11(11):3974–86.CrossRefPubMedGoogle Scholar
  9. 9.
    Cooper WA, Kohonen-Corish MR, McCaughan B, Kennedy C, Sutherland RL, Lee CS. Expression and prognostic significance of cyclin B1 and cyclin A in non-small cell lung cancer. Histopathology. 2009;55(1):28–36.CrossRefPubMedGoogle Scholar
  10. 10.
    Nozoe T, Korenaga D, Kabashima A, Ohga T, Saeki H, Sugimachi K. Significance of cyclin B1 expression as an independent prognostic indicator of patients with squamous cell carcinoma of the esophagus. Clin Cancer Res. 2002;8(3):817–22.PubMedGoogle Scholar
  11. 11.
    Takeno S, Noguchi T, Kikuchi R, Uchida Y, Yokoyama S, Muller W. Prognostic value of cyclin B1 in patients with esophageal squamous cell carcinoma. Cancer. 2002;94(11):2874–81.CrossRefPubMedGoogle Scholar
  12. 12.
    Aaltonen K, Amini RM, Heikkila P, Aittomaki K, Tamminen A, et al. High cyclin B1 expression is associated with poor survival in breast cancer. Br J Cancer. 2009;100(7):1055–60.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Nimeus-Malmstrom E, Koliadi A, Ahlin C, Holmqvist M, Holmberg L, et al. Cyclin B1 is a prognostic proliferation marker with a high reproducibility in a population-based lymph node negative breast cancer cohort. Int J Cancer. 2010;127(4):961–7.PubMedGoogle Scholar
  14. 14.
    Horree N, van Diest PJ, van der Groep P, Sie-Go DM, Heintz AP. Progressive derailment of cell cycle regulators in endometrial carcinogenesis. J Clin Pathol. 2008;61(1):36–42.CrossRefPubMedGoogle Scholar
  15. 15.
    Milde-Langosch K, Bamberger AM, Goemann C, Rossing E, Rieck G, et al. Expression of cell-cycle regulatory proteins in endometrial carcinomas: correlations with hormone receptor status and clinicopathologic parameters. J Cancer Res Clin Oncol. 2001;127(9):537–44.CrossRefPubMedGoogle Scholar
  16. 16.
    Kayaselcuk F, Erkanli S, Bolat F, Seydaoglu G, Kuscu E, Demirhan B. Expression of cyclin H in normal and cancerous endometrium, its correlation with other cyclins, and association with clinicopathologic parameters. Int J Gynecol Cancer. 2006;16(1):402–8.CrossRefPubMedGoogle Scholar
  17. 17.
    Rijcken F, van der Zee A, van der Sluis T, Boersma-van Ek W, Kleibeuker J, Hollema H. Cell cycle regulators and apoptosis-associated proteins in relation to proliferative activity and degree of apoptosis in HNPCC versus sporadic endometrial carcinoma. Histopathology. 2006;48(3):275–85.CrossRefPubMedGoogle Scholar
  18. 18.
    Shih HC, Shiozawa T, Kato K, Imai T, Miyamoto T, et al. Immunohistochemical expression of cyclins, cyclin-dependent kinases, tumor-suppressor gene products, ki-67, and sex steroid receptors in endometrial carcinoma: positive staining for cyclin A as a poor prognostic indicator. Hum Pathol. 2003;34(5):471–8.CrossRefPubMedGoogle Scholar
  19. 19.
    Yam CH, Fung TK, Poon RY. Cyclin A in cell cycle control and cancer. Cell Mol Life Sci. 2002;59(8):1317–26.CrossRefPubMedGoogle Scholar
  20. 20.
    Xu XL, Chen SZ, Chen W, Zheng WH, Xia XH, et al. The impact of cyclin D1 overexpression on the prognosis of ER-positive breast cancers: a meta-analysis. Breast Cancer Res Treat. 2013;139(2):329–39.CrossRefPubMedGoogle Scholar
  21. 21.
    Huang LN, Wang DS, Chen YQ, Li W, Hu FD, et al. Meta-analysis for cyclin E in lung cancer survival. Clin Chim Acta. 2012;413(7–8):663–8.CrossRefPubMedGoogle Scholar
  22. 22.
    Gould Rothberg BE, Bracken MB, Rimm DL. Tissue biomarkers for prognosis in cutaneous melanoma: a systematic review and meta-analysis. J Natl Cancer Inst. 2009;101(7):452–74.CrossRefPubMedGoogle Scholar
  23. 23.
    Begnami MD, Fregnani JH, Nonogaki S, Soares FA. Evaluation of cell cycle protein expression in gastric cancer: cyclin B1 expression and its prognostic implication. Hum Pathol. 2010;41(8):1120–7.CrossRefPubMedGoogle Scholar
  24. 24.
    Shin JU, Lee CH, Lee KT, Lee KH, Kim KM, et al. Prognostic significance of ATM and cyclin B1 in pancreatic neuroendocrine tumor. Tumor Biol. 2012;33(5):1645–51.CrossRefGoogle Scholar
  25. 25.
    Santala S, Talvensaari-Mattila A, Soini Y, Honkavuori-Toivola M, Santala M. High expression of cyclin A is associated with poor prognosis in endometrial endometrioid adenocarcinoma. Tumor Biol. 2014;35(6):5395–9.CrossRefGoogle Scholar
  26. 26.
    Ahmed A, Zamba G, DeGeest K, Lynch CF. The impact of surgery on survival of elderly women with endometrial cancer in the SEER program from 1992–2002. Gynecol Oncol. 2008;111(1):35–40.CrossRefPubMedGoogle Scholar
  27. 27.
    Benedetti Panici P, Basile S, Salerno MG, Di Donato V, Marchetti C, et al. Secondary analyses from a randomized clinical trial: age as the key prognostic factor in endometrial carcinoma. Am J Obstet Gynecol. 2014;210(4):363.e1–10.CrossRefGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Simi Santala
    • 1
  • Anne Talvensaari-Mattila
    • 1
  • Ylermi Soini
    • 2
    • 3
  • Markku Santala
    • 1
  1. 1.Department of Obstetrics and GynecologyOulu University HospitalOuluFinland
  2. 2.Department of PathologyOulu University HospitalOuluFinland
  3. 3.Department of Pathology and Forensic Medicine, Institute of Clinical Medicine, Pathology and Forensic Medicine, School of Medicine, Cancer Center of Eastern FinlandUniversity of Eastern FinlandKuopioFinland

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