title: Telomerase activity in breast cancer patients: association with poor prognosis and more aggressive phenotype.
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.
authors.affiliation: Department of Oncology, Division of Pathophysiology and Experimental Oncology, University Hospital Center Zagreb, Kišpatićeva 12, 10000, Zagreb, Croatia.
authors.forename: Ana
authors.initials: A
authors.lastname: Kulić
authors.affiliation: Department of Oncology, Division of Medical Oncology, University Hospital Center Zagreb, Zagreb, Croatia.|School of Medicine, University of Zagreb, Zagreb, Croatia.
authors.forename: Natalija Dedić
authors.initials: ND
authors.lastname: Plavetić
authors.affiliation: Croatian Academy of Science and Arts, Zagreb, Croatia.
authors.forename: Stjepan
authors.initials: S
authors.lastname: Gamulin
authors.affiliation: Department of Pathology, University Hospital Center Zagreb, Zagreb, Croatia.|School of Medicine, University of Zagreb, Zagreb, Croatia.
authors.forename: Jasminka
authors.initials: J
authors.lastname: Jakić-Razumović
authors.affiliation: Department of Oncology, Division of Medical Oncology, University Hospital Center Zagreb, Zagreb, Croatia.|School of Medicine, University of Zagreb, Zagreb, Croatia.
authors.forename: Damir
authors.initials: D
authors.lastname: Vrbanec
authors.affiliation: Department of Oncology, Division of Pathophysiology and Experimental Oncology, University Hospital Center Zagreb, Kišpatićeva 12, 10000, Zagreb, Croatia. majas@irb.hr.|School of Medicine, University of Zagreb, Zagreb, Croatia. majas@irb.hr.
authors.forename: Maja
authors.initials: M
authors.lastname: Sirotković-Skerlev
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000201:enzymology* / Q000601:surgery; D018572:Disease-Free Survival; D004789:Enzyme Activation / Q000502:physiology; D005260:Female; D006801:Humans; D008875:Middle Aged; D010641:Phenotype; D011379:Prognosis; D019098:Telomerase / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D019098:Telomerase
keywords: Aggressive phenotype; Breast cancer; Prognosis; Telomerase activity
references.citation: Eur J Surg Oncol. 2000 Feb;26(1):30-3
references.pmid: 10718176
references.citation: J Natl Cancer Inst. 1997 Dec 17;89(24):1874-81
references.pmid: 9414175
references.citation: Cancer Res. 1977 Jun;37(6):1733-8
references.pmid: 404036
references.citation: Breast Cancer Res. 2011 Jun 06;13(3):R56
references.pmid: 21645396
references.citation: Curr Pharm Des. 2014;20(41):6361-74
references.pmid: 24975603
references.citation: Br J Cancer. 2000 Oct;83(7):841-6
references.pmid: 10970682
references.citation: Oncogene. 1999 Jun 3;18(22):3407-14
references.pmid: 10362362
references.citation: Tumour Biol. 2013 Jun;34(3):1371-80
references.pmid: 23558965
references.citation: Curr Pharm Des. 2014;20(41):6386-403
references.pmid: 24975608
references.citation: Cell. 2011 Mar 4;144(5):646-74
references.pmid: 21376230
references.citation: Clin Sci (Lond). 2011 May;120(10):427-40
references.pmid: 21271986
references.citation: J Clin Oncol. 1999 Oct;17(10):3075-81
references.pmid: 10506602
references.citation: Science. 1994 Dec 23;266(5193):2011-5
references.pmid: 7605428
references.citation: Cancer Res. 1999 Dec 1;59(23):5917-21
references.pmid: 10606235
references.citation: Med Oncol. 2003;20(2):117-26
references.pmid: 12835514
references.citation: Int J Cancer. 1999 Oct 22;84(5):516-20
references.pmid: 10502730
references.citation: Eur J Cancer. 1997 Apr;33(5):787-91
references.pmid: 9282118
references.citation: Mol Cell Biol. 2004 Jan;24(1):25-35
references.pmid: 14673140
references.citation: Neoplasma. 2001;48(4):267-73
references.pmid: 11712677
references.citation: J Cell Mol Med. 2011 Jun;15(6):1227-38
references.pmid: 21352473
references.citation: Breast. 1999 Aug;8(4):208-11
references.pmid: 14731443
references.citation: Mol Cell Biol. 2011 Jul;31(13):2605-17
references.pmid: 21536653
references.citation: Eur J Cancer. 1997 Apr;33(5):781-6
references.pmid: 9282117
references.citation: Curr Pharm Des. 2014;20(41):6438-51
references.pmid: 24975610
references.citation: Cancer Res. 2010 Nov 1;70(21):8684-94
references.pmid: 20837664
references.citation: J Pathol. 2002 Oct;198(2):181-9
references.pmid: 12237877
references.citation: Gene. 2012 May 1;498(2):135-46
references.pmid: 22381618
references.citation: J Natl Cancer Inst. 1996 Jan 17;88(2):116-22
references.pmid: 8537972
references.citation: J Biol Chem. 1951 Nov;193(1):265-75
references.pmid: 14907713
references.citation: Int J Cancer. 1996 Aug 22;69(4):301-6
references.pmid: 8797872
references.citation: EMBO J. 1995 Sep 1;14(17):4240-8
references.pmid: 7556065
references.citation: Int J Cancer. 1998 Aug 21;79(4):343-8
references.pmid: 9699524
references.citation: Clin Chim Acta. 2006 Sep;371(1-2):25-31
references.pmid: 16616059
references.citation: Int J Cancer. 1998 Feb 20;79(1):8-12
references.pmid: 9495350
references.citation: Anticancer Res. 2005 May-Jun;25(3B):1927-30
references.pmid: 16158927
references.citation: Adv Anat Pathol. 2004 Sep;11(5):262-8
references.pmid: 15322492