Tumor Biology

, Volume 36, Issue 5, pp 3441–3445 | Cite as

Survinin expression in patients with breast cancer during chemotherapy

  • S. R. Marsicano
  • R. K. Kuniyoshi
  • F. S. Gehrke
  • B. C. A. Alves
  • L. A. Azzalis
  • F. L. A. Fonseca
Research Article

Abstract

Breast cancer (BC) is the second most common cancer worldwide and the first among women. If early diagnosed and treated, this disease has a good prognosis. However, it is believed that 90 % of all patients who have had cancer died due to metastatic disease, which highlights the need for a marker which allows the detection of latent cancer cells spread from the primary tumor. The objective of this study was to investigate the expression of survinin in peripheral blood of patients with breast cancer at diagnosis and during chemotherapy aiming correlation with minimal residual disease, clinical and pathological findings. The study included 40 patients with breast cancer and 12 healthy donors as a comparison group. Survinin expression was verified by real-time PCR. For diagnosis, survinin expression cutoff point was 1.05; considering this cutoff point, we obtained a test sensitivity of 85.3 %, specificity of 75.0 %, positive predictive value of 90.6 %, negative predictive value of 64.3 %, and accuracy of 82.6 %. There was statistical significance between groups (patients × control group), presenting to patients a significantly higher value than the control group (p < 0.001). Patients that presented at the diagnosis a survinin gene expression ≥1.05 are 17 times more likely to develop metastatic disease.

Keywords

Neoplasm Survinin Metastatic disease Prognostic marker 

Notes

Acknowledgments

This work was supported by the FAPESP grant 2011/22746-9.

Conflicts of interest

None

References

  1. 1.
    Silva APR, Noronha CP, Silva JLO, Ferreira JMO, Oliveira JFP, Santos MO. Estimativa 2012 Incidência de Câncer no Brasil. 2012. http://portal.saude.sp.gov.br/resources/ses/perfil/gestor/homepage/estimativas-de-incidencia-de-cancer-2012/estimativas_incidencia_cancer_2012.pdf. Accessed 03 Oct 2014.
  2. 2.
    Guimarães BM, Silva C, Noronha CP, Silva GS, Oliveira JFP, Pereira KA. Estimativa 2014 Incidência de Câncer no Brasil. 2014. http://www.inca.gov.br/estimativa/2014/estimativa-24012014.pdf. Accessed 27 Jan 2014.
  3. 3.
    Yu M, Stott S, Toner M, Maheswaran S, Haber DA. Circulating tumor cells: isolation and approaches to characterization. J Cell Biol. 2011;192:373–82.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Pantel K, Panabie CA. Circulating tumor cells in cancer patients: challenges and perspectives. Trends Mol Med. 2010;16:398–406.CrossRefPubMedGoogle Scholar
  5. 5.
    Yoshihara RN, Teixeira BM, Adami F, Kuniyoshi RK, Alves BCA, Gehrke FS, et al. Circulating tumor cell detection during chemotherapy in patients with breast cancer is not associated with plasma homocysteine levels. Tumor Biol. 2013;34:2937–41.CrossRefGoogle Scholar
  6. 6.
    Ambrosini G, Adida C, Altieri DC. A novel anti-apoptosis gene, survivin, expressed in cancer and lymphoma. Nat Med. 1997;3:917–21.CrossRefPubMedGoogle Scholar
  7. 7.
    Altieri DC. Survivin, cancer networks and pathway-directed drug discovery. Nat Rev Cancer. 2008;8:61–70.CrossRefPubMedGoogle Scholar
  8. 8.
    Jha K, Shukla M, Pandey M. Survivin expression and targeting in breast cancer. Surg Oncol. 2012;21:125–31.CrossRefPubMedGoogle Scholar
  9. 9.
    Church DN, Talbot DC. Survivin in solid tumors: rationale for development of inhibitors. Springer Curr Oncol Rep. 2012;14:120–8.CrossRefGoogle Scholar
  10. 10.
    Dohi T, Beltrami E, Wall NR, Plescia J, Altieri DC. Mitochondrial survivin inhibits apoptosis and promotes tumorigenesis. J Clin Invest. 2004;114:1117–27.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Span PN, Heijnen VCGT, Heuvel JJTM, Kok JB, Foekens JA, Sweep FCGJ. Do the survivin (BIRC5) splice variants modulate or add to the prognostic value of total survivin in breast cancer? Clin Chem. 2006;52:1693–700.CrossRefPubMedGoogle Scholar
  12. 12.
    Kelly AE, Ghenoiu C, Xue JZ, Zierhut C, Kimura H, et al. Survivin reads phosphorylated histone H3 threonine 3 to activate the mitotic kinase Aurora B. Science. 2010 Science 8 October 2010: Vol. 330 no. 6001 pp. 235–9.Google Scholar
  13. 13.
    Yamagishi Y, Honda T, Tanno Y, Watanabe Y. Two histone marks establish themselves the inner centromere and chromosome bi-orientation. Science. 2010;330:235–9.CrossRefGoogle Scholar
  14. 14.
    Mehrotra S, Languino LR, Raskett CM, Mercurio AM, Dohi T, Altieri DC. IAP regulation of metastasis. Cancer Cell. 2010;17:53–64.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Tran J, Master Z, Yu JL, Rak J, Dumont DJ, Kerberl RS. A role for survivin in chemoresistance of endothelial cells mediated by VEGF. PNAS. 2002;99:4349–54.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Caldas H, Fangusaro JR, Boue DR, Holloway MP, Altura RA. Dissecting the role of DeltaEx3 endothelial survivin in angiogenesis. Blood. 2007;109:1479–89.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Johnen G, Gawrych K, Bontrup H, Pesch B, Taeger D, Banek S, et al. Performance of survivin mRNA as a biomarker for bladder cancer in the prospective study UroScreen. Plos One. 2012. doi: 10.1371/journal.pone.0035363.
  18. 18.
    Marsicano SR, Pinto JLF, Delgado PO, Coelho PG, Fonseca FLA. Systemic chemotherapy-induced microsatellite instability in the mononuclear cell fraction of women with breast cancer can be reproduced in vitro and abrogated by amifostine. J Pharm Pharmacol. 2010;62:931–4.CrossRefPubMedGoogle Scholar
  19. 19.
    Yamashita EK, Teixeira BM, Yoshihara RN, Kuniyoshi RK, Alves BCA, Gehrke FS, et al. Systemic chemotherapy interferes in homocysteine metabolism in breast cancer patients. J Clin Lab Anal. 2014;28:157–62.CrossRefPubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • S. R. Marsicano
    • 1
  • R. K. Kuniyoshi
    • 1
  • F. S. Gehrke
    • 1
  • B. C. A. Alves
    • 1
  • L. A. Azzalis
    • 2
  • F. L. A. Fonseca
    • 1
    • 2
  1. 1.Oncology and Hematology Department-ABC Medical SchoolSanto AndréBrazil
  2. 2.Biological Sciences DepartmentFederal University of São PauloDiademaBrazil

Personalised recommendations