Tumor Biology

, Volume 37, Issue 1, pp 749–762 | Cite as

A comprehensive analysis of CDC20 overexpression in common malignant tumors from multiple organs: its correlation with tumor grade and stage

  • Mariana F. Gayyed
  • Nehad M. R. Abd El-Maqsoud
  • Ehab Rifat Tawfiek
  • Saad Abdelnaby A. El Gelany
  • Mohamed Fathy Abdel Rahman
Original Article


High expression of cell division cycle 20 homolog (CDC20), a key component of the spindle assembly checkpoint (SAC), has been reported in various malignancies and plays a vital role in tumorigenesis and progression. The goal of this study was to evaluate the utility of CDC20 immunostaining in a wide range of malignant tumors. CDC20 immunohistochemistry was evaluated in normal tissues and compared to the most frequently occurring malignant tumors in these tissues (bladder, breast, cervical, colonic, endometrial, gastric, head and neck, liver, lung, ovarian, pancreatic, prostatic, renal, thyroid carcinomas, and testicular seminoma). Normal/non-neoplastic tissues showed positive CDC20 expression in 19.44 % of all examined cases. CDC20 staining was negative in normal and non-neoplastic tissues from the bladder, cervix, liver, stomach, and thyroid. From the all malignant tumors examined 55.7 % showed high CDC20 expression while low expression was found in 44.3 %. High expression of CDC20 was associated with high tumor grade in the bladder (p = 0.027), cervical (p = 0.032), colonic (p = 0.026), endometrial (p = 0.016), gastric (p = 0.033), liver (p = 0.028), ovarian (p = 0.044), prostatic (p = 0.040), and renal (p = 0.048) carcinomas. There was a significant correlation between high CDC20 expression and advanced tumor stage in carcinoma of the breast, colon, endometrium, and prostate (p = 0.021, p = 0.040, p = 0.047, p = 0.031, respectively). CDC20 expression may be useful as a biomarker of tumor prognosis and as a therapeutic target of human cancer.


CDC20 Immunohistochemistry Normal/non-neoplastic tissues Carcinomas 


Conflicts of interest



  1. 1.
    Lengauer C, Kinzler KW, Vogelstein B. Genetic instabilities in human cancers. Nature. 1998;396(6712):643–9.CrossRefPubMedGoogle Scholar
  2. 2.
    Suijkerbuijk SJ, Kops GJ. Preventing aneuploidy: the contribution of mitotic checkpoint proteins. Biochim Biophys Acta. 2008;1786(1):24–31.PubMedGoogle Scholar
  3. 3.
    Hanahan D, Weinberg RA. The hallmarks of cancer. Cell. 2000;100:57–70.CrossRefPubMedGoogle Scholar
  4. 4.
    Jallepalli PV, Lengauer C. Chromosome segregation and cancer: cutting through the mystery. Nat Rev Cancer. 2001;1(2):109–17.CrossRefPubMedGoogle Scholar
  5. 5.
    Rajagopalan H, Lengauer C. Aneuploidy and cancer. Nature. 2004;432(7015):338–41.CrossRefPubMedGoogle Scholar
  6. 6.
    Bharadwaj R, Yu H. The spindle checkpoint, aneuploidy, and cancer. Oncogene. 2004;23(11):2016–27.CrossRefPubMedGoogle Scholar
  7. 7.
    Li Y, Benezra R. Identification of a human mitotic checkpoint gene: hsMAD2. Science. 1996;274(5285):246–8.CrossRefPubMedGoogle Scholar
  8. 8.
    Amon A. The spindle checkpoint. Curr Opin Genet Dev. 1999;9(1):69–75.CrossRefPubMedGoogle Scholar
  9. 9.
    Iwanaga Y, Kasai T, Kibler K, Jeang KT. Characterization of regions in hsMAD1 needed for binding hsMAD2. A polymorphic change in an hsMAD1 leucine zipper affects MAD1–MAD2 interaction and spindle checkpoint function. J Biol Chem. 2002;277(34):31005–13.CrossRefPubMedGoogle Scholar
  10. 10.
    Li R. Bifurcation of the mitotic checkpoint pathway in budding yeast. Proc Natl Acad Sci U S A. 1999;96(9):4989–94.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Haruki N, Saito H, Harano T, Nomoto S, Takahashi T, Osada H, et al. Molecular analysis of the mitotic checkpoint genes BUB1, BUBR1 and BUB3 in human lung cancers. Cancer Lett. 2001;16292:201–5.CrossRefGoogle Scholar
  12. 12.
    Hernando E, Orlow I, Liberal V, Nohales G, Benezra R, CordonCardo C. Molecular analyses of the mitotic checkpoint components hsMAD2, hBUB1 and hBUB3 in human cancer. Int J Cancer. 2001;95(4):223–7.CrossRefPubMedGoogle Scholar
  13. 13.
    Ouyang B, Knauf JA, Ain K, Nacev B, Fagin JA. Mechanisms of aneuploidy in thyroid cancer cell lines and tissues:evidence for mitotic checkpoint dysfunction without mutations in BUB1 and BUBR1. Clin Endocrinol (Oxf). 2002;56(3):341–50.CrossRefGoogle Scholar
  14. 14.
    Doak SH, Jenkins GJ, Parry EM, Griffiths AP, Baxter JN, Parry JM. Differential expression of the MAD2, BUB1 and HSP27 genes in Barrett’s oesophagus—their association with aneuploidy and neoplastic progression. Mutat Res. 2004;547(1–2):133–44.CrossRefPubMedGoogle Scholar
  15. 15.
    Jeong SJ, Shin HJ, Kim SJ, Ha GH, Cho BI, Baek KH, et al. Transcriptional abnormality of the hsMAD2 mitotic checkpoint gene is a potential link to hepatocellular carcinogenesis. Cancer Res. 2004;64(23):8666–73.CrossRefPubMedGoogle Scholar
  16. 16.
    Sze KM, Ching YP, Jin DY, Ng IO. Association of MAD2 expression with mitotic checkpoint competence in hepatoma cells. J Biomed Sci. 2004;11(6):920–7.CrossRefPubMedGoogle Scholar
  17. 17.
    Kienitz A, Vogel C, Morales I, Muller R, Bastians H. Partial downregulation of MAD1 causes spindle checkpoint inactivation and aneuploidy, but does not confer resistance towards taxol. Oncogene. 2004;24(26):4301–10.CrossRefGoogle Scholar
  18. 18.
    Wasch R, Engelbert D. Anaphase-promoting complex dependent proteolysis of cell cycle regulators and genomic instability of cancer cells. Oncogene. 2005;24(1):1–10.CrossRefPubMedGoogle Scholar
  19. 19.
    Musacchio A, Salmon ED. The spindle-assembly checkpoint in space and time. Nat Rev Mol Cell Biol. 2007;8(5):379–93.CrossRefPubMedGoogle Scholar
  20. 20.
    Kim S, Yu H. Mutual regulation between the spindle checkpoint and APC/C. Semin Cell Dev Biol. 2011;22(6):551–8.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Sudakin V, Chan GK, Yen TJ. Checkpoint inhibition of the APC/C in HeLa cells is mediated by a complex of BUBR1, BUB3, CDC20, and MAD2. J Cell Biol. 2001;154(5):925–36.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Howell BJ, Moree B, Farrar EM, Stewart S, Fang G, Salmon ED. Spindle checkpoint protein dynamics at kinetochores in living cells. Curr Biol. 2004;14(11):953–64.CrossRefPubMedGoogle Scholar
  23. 23.
    Chang DZ, Ma Y, Ji B, Liu Y, Hwu P, Abbruzzese JL, et al. Increased CDC20 expression is associated with pancreatic ductal adenocarcinoma differentiation and progression. J Hematol Oncol. 2012;4:5–15.CrossRefGoogle Scholar
  24. 24.
    Kato T, Daigo Y, Aragaki M, Ishikawa K, Sato M, Kaji M. Overexpression of CDC20 predicts poor prognosis in primary non small cell lung cancer patients. J Surg Oncol. 2012;106(4):423–30.CrossRefPubMedGoogle Scholar
  25. 25.
    Choi JW, Kim Y, Lee JH, Kim YS. High expression of spindle assembly checkpoint proteins CDC20 and MAD2 is associated with poor prognosis in urothelial bladder cancer. Virchows Arch. 2013;463(5):681–7.CrossRefPubMedGoogle Scholar
  26. 26.
    Wu WJ, Hu KS, Wang DS, Zeng ZL, Zhang DS, Chen DL, et al. CDC20 overexpression predicts a poor prognosis for patients with colorectal cancer. J Transl Med. 2013;11:142.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Moura IM, Delgado ML, Silva PM, Lopes CA, do Amaral JB, Monteiro LS. High CDC20 expression is associated with poor prognosis in oral squamous cell carcinoma. J Oral Pathol Med. 2014;43(3):225–31.CrossRefPubMedGoogle Scholar
  28. 28.
    Izawa D, Pines J. The mitotic checkpoint complex binds a second CDC20 to inhibit activate APC/C. Nature. 2015;517(7536):631–4.CrossRefPubMedGoogle Scholar
  29. 29.
    Hongtao Y. Cdc20. A WD40 activator for a cell cycle degradation machine. Mol Cell. 2007;27(1):3–16.CrossRefGoogle Scholar
  30. 30.
    Mondal G, Sengupta S, Panda CK, Gollin SM, Saunders WS, Roychoudhury S. Overexpression of CDC20 leads to impairment of the spindle assembly checkpoint and aneuploidization in oral cancer. Carcinogenesis. 2007;28(1):81–92.CrossRefPubMedGoogle Scholar
  31. 31.
    Clarke DJ, Segal M, Andrews CA, Rudyak SG, Jensen S, Smith K, et al. S-phase checkpoint controls mitosis via an APC-independent CDC20p function. Nat Cell Biol. 2003;5(10):928–35.CrossRefPubMedGoogle Scholar
  32. 32.
    Shi J, Orth JD, Mitchison T. Cell type variation in responses to antimitotic drugs that target microtubules and kinesin-5. Cancer Res. 2008;68(9):3269–76.CrossRefPubMedGoogle Scholar
  33. 33.
    Gascoigne KE, Taylor SS. Cancer cells display profound intra- and interline variation following prolonged exposure to antimitotic drugs. Cancer Cell. 2008;14(2):111–22.CrossRefPubMedGoogle Scholar
  34. 34.
    Huang HC, Shi J, Orth JD, Mitchison TJ. Evidence that mitotic exit is a better cancer therapeutic target than spindle assembly. Cancer Cell. 2009;16(4):347–58.CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Kidokoro T, Tanikawa C, Furukawa Y, Katagiri T, Nakamura Y, Matsuda K. CDC20, a potential cancer therapeutic target, is negatively regulated by p53. Oncogene. 2008;27(11):1562–71.CrossRefPubMedGoogle Scholar
  36. 36.
    Ding ZY, Wu HR, Zhang JM, Huang GR, Ji DD. Expression characteristics of CDC20 in gastric cancer and its correlation with poor prognosis. Int J Clin Exp Pathol. 2014;7(2):722–7.PubMedPubMedCentralGoogle Scholar
  37. 37.
    Karra H, Repo H, Ahonen I, Löyttyniemi E, Pitkänen R, Lintunen M, et al. CDC20 and securin overexpression predict short-term breast cancer survival. Br J Cancer. 2014;110(12):2905–13.CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Kim Y, Choi JW, Lee JH, Kim YS. MAD2 and CDC20 are upregulated in high-grade squamous intraepithelial lesions and squamous cell carcinomas of the uterine cervix. Int J Gynecol Pathol. 2014;33(5):517–23.CrossRefPubMedGoogle Scholar
  39. 39.
    Li J, Gao JZ, Du JL, Huang ZX, Wei LX. Increased CDC20 expression is associated with development and progression of hepatocellular carcinoma. Int J Oncol. 2014;45(4):1547–55.PubMedGoogle Scholar
  40. 40.
    Ouellet VGM, Le Page C, Filali-Mouhim A, Lussier C, Tonin PN, Provencher DM, et al. Tissue array analysis of expression microarray candidates identifies markers associated with tumor grade and outcome in serous epithelial ovarian cancer. Int J Cancer. 2006;119(3):599–607.CrossRefPubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Mariana F. Gayyed
    • 1
  • Nehad M. R. Abd El-Maqsoud
    • 1
  • Ehab Rifat Tawfiek
    • 2
  • Saad Abdelnaby A. El Gelany
    • 3
  • Mohamed Fathy Abdel Rahman
    • 4
  1. 1.Department of Pathology, Faculty of MedicineMinia UniversityEl-MiniaEgypt
  2. 2.Department of Urology, Faculty of MedicineMinia UniversityEl-MiniaEgypt
  3. 3.Department of Obstetrics and Gynecology, Faculty of MedicineMinia UniversityEl-MiniaEgypt
  4. 4.Department of Surgery, Faculty of MedicineMinia UniversityEl-MiniaEgypt

Personalised recommendations