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Telomerase activity in breast cancer patients: association with poor prognosis and more aggressive phenotype

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Abstract

Telomerase expression is an important mechanism of tumor unlimited replicative potential. The aim of this study was to evaluate prognostic impact of telomerase activity in breast cancer patients and to correlate telomerase activity with established prognostic factors. We analyzed tissue of 102 malignant breast lesions and 20 healthy breast tissues. Telomerase activity was determined by telomeric repeat amplification protocol assay. Telomerase activity was present in 77 (75.49 %) of 102 breast cancers. Telomerase activity in breast cancers was statistically significantly higher in comparison with the activity in normal breast tissue. The levels of telomerase activity were significantly positively correlated with tumor size, axillary nodal status, histological grade, HER-2/neu protein expression in tumor tissue and expression of the nuclear antigen Ki-67. A statistically significant negative correlation was found between the presence of ER and telomerase activity. There was no correlation between telomerase activity and concentration of PR or the age of patients. Kaplan–Meier analysis showed that patients with higher telomerase activity had significantly shorter 10-year disease-free survival (p < 0.0001) and 10-year overall survival (p < 0.0001) than those with lower telomerase activity. These results were confirmed by logistic regression analysis. Our results support the prognostic role of telomerase activity and its relationship with the more aggressive phenotype of breast cancer.

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References

  1. Hayflick L. The illusion of cell immortality. Br J Cancer. 2000;83:841–6.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  2. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144:646–74.

    Article  CAS  PubMed  Google Scholar 

  3. Zhu H, Belcher M, van der Harst P. Healthy aging and disease: role for telomere biology? Clin Sci (Lond). 2011;120:427–40.

    Article  Google Scholar 

  4. Daniel M, Peek GW, Tollefsbol TO. Regulation of the human catalytic subunit of telomerase (hTERT). Gene. 2012;498:135–46.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  5. Li AY, Lin HH, Kuo CY, Shih HM, Wang CC, Yen Y, et al. High-mobility group A2 protein modulates hTERT transcription to promote tumorigenesis. Mol Cell Biol. 2011;31:2605–17.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  6. Reddel RR. Telomere maintenance mechanisms in cancer: clinical implications. Curr Pharm Des. 2014;20:6361–74.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  7. Kim NW. Clinical implications of telomerase in cancer. Eur J Cancer. 1997;33:781–6.

    Article  CAS  PubMed  Google Scholar 

  8. Shay JW, Bacchetti S. A survey of telomerase activity in human cancer. Eur J Cancer. 1997;33:787–91.

    Article  CAS  PubMed  Google Scholar 

  9. Bryan TM, Englezou A, Gupta J, Bacchetti S, Reddel RR. Telomere elongation in immortal human cells without detectable telomerase activity. EMBO J. 1995;14:4240–8.

    PubMed Central  CAS  PubMed  Google Scholar 

  10. Holysz H, Lipinska N, Paszel-Jaworska A, Rubis B. Telomerase as a useful target in cancer fighting-the breast cancer case. Tumour Biol. 2013;34:1371–80.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  11. Saretzki G. Extra-telomeric functions of human telomerase: cancer, mitochondria and oxidative stress. Curr Pharm Des. 2014;20:6386–403.

    Article  CAS  PubMed  Google Scholar 

  12. Heaphy CM, Meeker AK. The potential utility of telomere-related markers for cancer diagnosis. J Cell Mol Med. 2011;15:1227–38.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  13. Romaniuk A, Kopczynski P, Ksiazek K, Rubis B. Telomerase modulation in therapeutic approach. Curr Pharm Des. 2014;20:6438–51.

    Article  CAS  PubMed  Google Scholar 

  14. Tamakawa RA, Fleisig HB, Wong JM. Telomerase inhibition potentiates the effects of genotoxic agents in breast and colorectal cancer cells in a cell cycle-specific manner. Cancer Res. 2010;70:8684–94.

    Article  CAS  PubMed  Google Scholar 

  15. Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Mathers C, Rebelo M, et al. GLOBOCAN 2012 v1.0, cancer incidence and mortality worldwide: IARC CancerBase No. 11 [Internet]. Lyon, France: International Agency for Research on Cancer; 2013. http://globocan.iarc.fr. Accessed 8 Oct 2015.

  16. Croatian National Cancer Registry. Cancer incidence in Croatia 2012. Bulletin no. 37. http://www.hzjz.hr/wp-content/uploads/2013/11/Bilten-2012_final.pdf. Accessed 20 Dec 2015.

  17. Horwitz KB, Mcguire WL. Progesterone and progesterone receptors in experimental breast cancer. Cancer Res. 1977;37:1733–8.

    CAS  PubMed  Google Scholar 

  18. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin Phenol reagent. J Biol Chem. 1951;193:265–75.

    CAS  PubMed  Google Scholar 

  19. Kim NW, Piatyszek MA, Prowse KR, Harley CB, West MD, Ho PL, et al. Specific association of human telomerase activity with immortal cells and cancer. Science. 1994;266:2011–5.

    Article  CAS  PubMed  Google Scholar 

  20. Fajkus J. Detection of telomerase activity by the TRAP assay and its variants of alternatives. Clin Chim Acta. 2006;371:27–31.

    Article  Google Scholar 

  21. Hiyama E, Gollahon L, Kataoka T, Kuroi K, Yokoyama T, Gazdar AF, et al. Telomerase activity in human breast tumors. J Natl Cancer Inst. 1996;88:116–22.

    Article  CAS  PubMed  Google Scholar 

  22. Roos G, Nilsson P, Cajander S, Nielsen NH, Arnerlöv C, Landberg G. Telomerase activity in relation to p53 status and clinico-pathological parameters in breast cancer. Int J Cancer. 1998;79:343–8.

    Article  CAS  PubMed  Google Scholar 

  23. Mokbell K, Parris CN, Ghilchik M, Newbold RF. Telomerase activity in the human breast. Breast. 1999;8:208–11.

    Article  CAS  PubMed  Google Scholar 

  24. Mokbel KM, Parris CN, Ghilchik M, Amerasinghe CN, Newbold RF. Telomerase activity and lymphovascular invasion in breast cancer. Eur J Surg Oncol. 2000;26:30–3.

    Article  CAS  PubMed  Google Scholar 

  25. Baykal A, Rosen D, Zhou C, Liu J, Sahin AA. Telomerase in breast cancer: a critical evaluation. Adv Anat Pathol. 2004;11:262–8.

    Article  CAS  PubMed  Google Scholar 

  26. Hoos A, Hepp HH, Kaul S, Ahlert T, Bastert G, Wallwiener D. Telomerase activity correlates with tumor aggressiveness and reflects therapy effect in breast cancer. Int J Cancer. 1998;79:8–12.

    Article  CAS  PubMed  Google Scholar 

  27. Umbricht CB, Sherman ME, Dome J, Carey LA, Marks J, Kim N, et al. Telomerase activity in ductal carcinoma in situ and invasive breast cancer. Oncogene. 1999;18:3407–14.

    Article  CAS  PubMed  Google Scholar 

  28. Loveday RL, Greenman J, Drew PJ, Monson JR, Kerin MJ. Genetic changes associated with telomerase activity in breast cancer. Int J Cancer. 1999;84:516–20.

    Article  CAS  PubMed  Google Scholar 

  29. Sugino T, Yoshida K, Bolodeoku J, Tahara H, Buley I, Manek S, et al. Telomerase activity in human breast cancer and benign breast lesions: diagnostic applications in clinical specimens, including fine needle aspirates. Int J Cancer. 1996;69:301–6.

    Article  CAS  PubMed  Google Scholar 

  30. Carey LA, Kim NW, Goodman S, Marks J, Henderson G, Umbricht CB, et al. Telomerase activity and prognosis in primary breast cancers. J Clin Oncol. 1999;17:3075–81.

    CAS  PubMed  Google Scholar 

  31. Kalogeraki A, Kafousi M, Ieromonachou P, Giannikaki E, Vrekoussis T, Zoras O, et al. Telomerase activity as a marker of invasive ductal breast carcinomas on FNABs and relationship to other prognostic variables. Anticancer Res. 2005;25:1927–30.

    CAS  PubMed  Google Scholar 

  32. Kyo S, Takakura M, Kanaya T, Zhuo W, Fujimoto K, Nishio Y, et al. Estrogen activates telomerase. Cancer Res. 1999;59:5917–21.

    CAS  PubMed  Google Scholar 

  33. Goueli BS, Janknecht R. Upregulation of the catalytic telomerase subunit by the transcription factor ER81 and oncogenic HER2/Neu, Ras, or Raf. Mol Cell Biol. 2004;24:25–35.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  34. Clark GM, Osborne CK, Levitt D, Wu F, Kim NW. Telomerase activity and survival of patients with node-positive breast cancer. J Natl Cancer Inst. 1997;89:1874–81.

    Article  CAS  PubMed  Google Scholar 

  35. Simícková M, Nekulová M, Pecen L, Cernoch M, Vagundová M, Pacovský Z. Quantitative determination of telomerase activity in breast cancer and benign breast diseases. Neoplasma. 2001;48:267–73.

    PubMed  Google Scholar 

  36. Kimura M, Koida T, Yanagita Y. A study on telomerase activity and prognosis in breast cancer. Med Oncol. 2003;20:117–26.

    Article  CAS  PubMed  Google Scholar 

  37. Poremba C, Heine B, Diallo R, Heinecke A, Wai D, Schaefer KL, et al. Telomerase as a prognostic marker in breast cancer: high-throughput tissue microarray analysis of hTERT and hTR. J Pathol. 2002;198:181–9.

    Article  CAS  PubMed  Google Scholar 

  38. Lu L, Zhang C, Zhu G, Irwin M, Risch H, Menato G, et al. Telomerase expression and telomere length in breast cancer and their associations with adjuvant treatment and disease outcome. Breast Cancer Res. 2011;13:R56.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

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Acknowledgments

This work was supported by the Ministry of Science, Education and Sports, Republic of Croatia (Grant 108-1080058-0046).

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Authors and Affiliations

  1. Department of Oncology, Division of Pathophysiology and Experimental Oncology, University Hospital Center Zagreb, Kišpatićeva 12, 10000, Zagreb, Croatia

    Ana Kulić & Maja Sirotković-Skerlev

  2. Department of Oncology, Division of Medical Oncology, University Hospital Center Zagreb, Zagreb, Croatia

    Natalija Dedić Plavetić & Damir Vrbanec

  3. Croatian Academy of Science and Arts, Zagreb, Croatia

    Stjepan Gamulin

  4. Department of Pathology, University Hospital Center Zagreb, Zagreb, Croatia

    Jasminka Jakić-Razumović

  5. School of Medicine, University of Zagreb, Zagreb, Croatia

    Natalija Dedić Plavetić, Jasminka Jakić-Razumović, Damir Vrbanec & Maja Sirotković-Skerlev

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  1. Ana Kulić
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  2. Natalija Dedić Plavetić
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Correspondence to Maja Sirotković-Skerlev.

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All procedures performed in the study were in accordance with the ethical standards of the institution research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Kulić, A., Plavetić, N.D., Gamulin, S. et al. Telomerase activity in breast cancer patients: association with poor prognosis and more aggressive phenotype. Med Oncol 33, 23 (2016). https://doi.org/10.1007/s12032-016-0736-x

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  • DOI: https://doi.org/10.1007/s12032-016-0736-x

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