Skip to main content

Prognostic value of survivin and EGFR protein expression in triple-negative breast cancer (TNBC) patients

Targeted Oncology volume 9, pages 349–357 (2014)Cite this article

Abstract

Triple-negative breast cancer (TNBC) is a particular type of breast cancer which is characterized by its biological aggressiveness, worse prognosis, and lack of prognostic markers or therapeutic targets in contrast with hormonal receptor-positive and human epidermal growth factor receptor 2-positive (HER2+) breast cancers. We aimed to evaluate survivin and epidermal growth factor receptor (EGFR) expression and their prognostic value and determine their relationships with the clinicopathological parameters of TNBC. A total of 136 patients who had undergone a resection of primary TNBC were enrolled at the Third Affiliated Hospital of Harbin Medical University from March 2003 to September 2005. Expression of ER, PR, HER2, EGFR, and survivin was assessed by immunohistochemistry. The association of TNBC and other clinicopathological variables and the prognostic value of survivin and EGFR expression were evaluated. Survivin was expressed in 62 (45.6 %) cases and EGFR was expressed in 82 (60.3 %) cases. Survivin expression was associated with menopausal status (P = 0.011), tumor size (P = 0.037), and lymph node status (P = 0.001). EGFR expression was associated with menopausal status (P = 0.029), lymph node status (P = 0.004), P53 expression (P = 0.001), Ki-67 expression (P = 0.028), and lymphatic vascular invasion (P = 0.037). A multivariate analysis demonstrated that tumor size (hazard ratio (HR) 1.587, 95 % confidence interval (CI) 1.081–2.330, P = 0.018 for disease-free survival (DFS); HR 1.606, 95%CI 1.096–2.354, P = 0.015 for overall survival (OS)), lymph node status (HR 2.873, 95%CI 1.544–5.344, P = 0.001 for DFS; HR 2.915, 95%CI 1.553–5.471, P = 0.001 for OS), tumor grade (HR 1.914, 95%CI 1.218–3.007, P = 0.005 for DFS; HR 1.983, 95%CI 1.228–3.203, P = 0.005 for OS), EGFR (HR 3.008, 95%CI 1.331–6.792, P = 0.008 for DFS; HR 3.151, 95%CI 1.374–7.226, P = 0.007 for OS), and survivin (HR 1.573, 95%CI 1.087–2.277, P = 0.016 for DFS; HR 1.607, 95%CI 1.088–2.374, P = 0.017 for OS) were of prognostic significance for disease-free and overall survival. We draw a conclusion from the present study that survivin and EGFR expression are useful prognostic markers of TNBC and might be useful for molecular targeting therapy of TNBC treatment.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

43,34 €

Price includes VAT (Finland)
Tax calculation will be finalised during checkout.

Fig. 1
Fig. 2
Fig. 3

References

  1. Bauer KR, Brown M, Cress RD et al (2007) Descriptive analysis of estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and Her2-negative invasive breast cancer, the so-called triple-negative phenotype: a population-based study from the California cancer registry. Cancer 109(9):1721–1728

    PubMed  Article  Google Scholar 

  2. Kilburn LS, On Behalf of the TNT Trial Management Group (2008) Triple-negative breast cancer: a new area for phase III breast cancer clinical trials. Clin Oncol (R Coll Radiol) 20(1):35–39

    CAS  Article  Google Scholar 

  3. Perou CM, Sorlie T, Eisen MB et al (2000) Molecular portraits of human breast tumors. Nature 406:747–752

    CAS  PubMed  Article  Google Scholar 

  4. Kreike B, van Kouwenhove M, Horlings H et al (2007) Gene expression profiling and histopathological characterization of triple-negative/basal-like breast carcinomas. Breast Cancer Res 9:R65

    PubMed Central  PubMed  Article  Google Scholar 

  5. Buchholz TA, Tu X, Ang KK (2005) Epidermal growth factor receptor expression correlates with poor survival in patients who have breast carcinoma treated with doxorubicin-based neoadjuvant chemotherapy. Cancer 104:676–681

    CAS  PubMed  Article  Google Scholar 

  6. Tsutsui S, Ohno S, Murakami S (2002) Prognostic value of epidermal growth factor receptor (EGFR) and its relationship to the estrogen receptor status in 1029 patients with breast cancer. Breast Cancer Res Treat 71:67–75

    PubMed  Article  Google Scholar 

  7. O'Driscoll L, Linehan R, Kennedy SM et al (2003) Lack of prognostic significance of survivin, survivin-Delta Ex3, survivin-2B, galectin-3, bag-1, bax-alpha, and MRP-1 mRNAs in breast cancer. Cancer Lett 201:225–236

    PubMed  Article  Google Scholar 

  8. Tanaka K, Iwamoto S, Gon G et al (2000) Expression of survivin and its relationship to loss of apoptosis in breast carcinomas. Clin Cancer Res 6:127–134

    CAS  PubMed  Google Scholar 

  9. Guillamo JS, Bouard S, Valable S et al (2009) Molecular mechanisms underlying effects of epidermal growth factor receptor inhibition on invasion, proliferation, and angiogenesis in experimental glioma. Clin Cancer Res 15:3697–3704

    CAS  PubMed  Article  Google Scholar 

  10. Ryan BM, Konecny GE, Kahlert S et al (2006) Survivin expression in breast cancer predicts clinical outcome and is associated with HER2, VEGF, urokinase plasminogen activator and PAI-1. Ann Oncol 17:597–604

    CAS  PubMed  Article  Google Scholar 

  11. Duckett CS, Nava VE, Gedrich RW et al (1996) A conserved family of cellular genes related to the baculovirus iap gene and encoding apoptosis inhibitors. EMBO J 14:2685–2694

    Google Scholar 

  12. Li F, Ling X (2006) Survivin study: an update of “what is the next wave”? J Cell Physiol 208:476–486

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  13. Kajiwara Y, Yamasaki F, Hama S et al (2003) Expression of survivin in astrocytic tumors: correlation with malignant grade and prognosis. Cancer 97:1077–1083

    PubMed  Article  Google Scholar 

  14. Andersen MH, Thor SP (2002) Survivin: a universal tumor antigen. Histol Histopathol 17:669–675

    CAS  PubMed  Google Scholar 

  15. Korkola JE, Devries S, Fridlyand J et al (2003) Differentiation of lobular versus ductal breast carcinomas by expression microarray analysis. Cancer Res 63:7167–7175

    CAS  PubMed  Google Scholar 

  16. Fields AC, Cotsonis G, Sexton D et al (2004) Survivin expression in hepatocellualr carcinoma: correlation with proliferation, prognostic parameters, and outcome. Mod Pathol 17:1378–1385

    CAS  PubMed  Article  Google Scholar 

  17. Ferrandina G, Legge F, Martinelli E et al (2005) Survivin expression in ovarian cancer and its correlation with clinico-pathological, surgical and apoptosis-related parameters. Br J Cancer 92:271–277

    CAS  PubMed Central  PubMed  Google Scholar 

  18. Preuss SF, Weinell A, Molitor M et al (2008) Survivin and epidermal growth factor receptor expression in surgically treated oropharyngeal squamous cell carcinoma. Head Neck 30:1318–1324

    PubMed  Article  Google Scholar 

  19. Span PN, Sweep FC, Wiegerinck ET et al (2004) Survivin is an independent prognostic marker for risk stratification of breast cancer patients. Clin Chem 50:1986–1993

    CAS  PubMed  Article  Google Scholar 

  20. Kennedy SM, O'Driscoll L, Purcell R et al (2003) Prognostic importance of survivin in breast cancer. Br J Cancer 88:1077–1083

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  21. Altman DG, McShane LM, Sauerbrei W et al (2012) Reporting recommendations for tumor marker prognostic studies (REMARK): explanation and elaboration. BMC Med 10:51

    PubMed Central  PubMed  Article  Google Scholar 

  22. Guler G, Huebner K, Himmetoglu C et al (2009) Fragile histidine triad protein, WW domain-containing oxidoreductase protein Wwox, and activator protein 2gamma expression levels correlate with basal phenotype in breast cancer. Cancer 115:899–908

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  23. Lo muzio L, Pannone G, Staibano S et al (2003) Survivin expression in oral squamous cell. Br J Cancer 89:2244–2248

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  24. Riva C, Dainese E, Caprara G et al (2005) Immunohistochemical study of androgen receptors in breast carcinoma. Evidence of their frequent expression in lobular carcinoma. Virchows Arch 447:695–700

    CAS  PubMed  Article  Google Scholar 

  25. Agoff SN, Swanson PE, Linden H et al (2003) Androgen receptor expression in estrogen receptor-negative breast cancer. Immunohistochemical, clinical, and prognostic associations. Am J Clin Pathol 120:725–731

    CAS  PubMed  Article  Google Scholar 

  26. Hitt R, Echarri MJ (2006) Molecular biology in head and neck cancer. Clin Transl Oncol 8:776–779

    CAS  PubMed  Article  Google Scholar 

  27. Kogiku M, Ohsawa I, Matsumoto K et al (2008) Prognosis of glioma patients by combined immunostaining for survivin, Ki-67 and epidermal growth factor receptor. J Clin Neurosci 15:1198–1203

    CAS  PubMed  Article  Google Scholar 

  28. Zimmermann M, Zouhair A, Azria D et al (2006) The epidermal growth factor receptor (EGFR) in head and neck cancer: its role and treatment implications. Radiat Oncol 1:11

    PubMed Central  PubMed  Article  Google Scholar 

  29. Knauf JA (2011) Does the epidermal growth factor receptor play a role in the progression of thyroid cancer? Thyroid 21(11):1171–1174

    CAS  PubMed  Article  Google Scholar 

  30. Schiff BA, McMurphy AB, Jasser SA et al (2004) Epidermal growth factor receptor (EGFR) is overexpressed in anaplastic thyroid cancer and the EGFR inhibitor gefitinib inhibits the growth of anaplastic thyroid cancer. Clin Cancer Res 10:8594–8602

    CAS  PubMed  Article  Google Scholar 

  31. Ludovini V, Bellezza G, Pistola L et al (2009) High coexpression of both insulin-like growth factor receptor-1 (IGFR-1) and epidermal growth factor receptor (EGFR) is associated with shorter disease-free survival in resected non-small-cell lung cancer patients. Ann Oncol 20:842–849

    CAS  PubMed  Article  Google Scholar 

  32. Spano JP, Lagorce C, Atlan D et al (2005) Impact of EGFR expression on colorectal cancer patient prognosis and survival. Ann Oncol 16:102–108

    PubMed  Article  Google Scholar 

  33. Wang X, Zhang S, MacLennan GT et al (2007) Epidermal growth factor receptor protein expression and gene amplification in small cell carcinoma of the urinary bladder. Clin Cancer Res 13:953–957

    CAS  PubMed  Article  Google Scholar 

  34. Leibl S, Zigeuner R, Hutterer G et al (2008) EGFR expression in urothelial carcinoma of the upper urinary tract is associated with disease progression and metaplastic morphology. APMIS 116:27–32

    PubMed  Article  Google Scholar 

  35. Chow NH, Chan SH, Tzai TS et al (2001) Expression profiles of ErbB family receptors and prognosis in primary transitional cell carcinoma of the urinary bladder. Clin Cancer Res 7:1957–1962

    CAS  PubMed  Google Scholar 

  36. Stadlmann S, Gueth U, Reiser U et al (2006) Epithelial growth factor receptor status in primary and recurrent ovarian cancer. Mod Pathol 19:607–610

    CAS  PubMed  Article  Google Scholar 

  37. Rimawi MF, Shetty PB, Weiss HL et al (2010) Epidermal growth factor receptor expression in breast cancer association with biologic phenotype and clinical outcomes. Cancer 116:1234–1242

    PubMed Central  PubMed  Article  Google Scholar 

  38. Dua R, Zhang J, Nhonthachit P et al (2010) EGFR over-expression and activation in high HER2, ER negative breast cancer cell line induces trastuzumab resistance. Breast Cancer Res Treat 122:685–697

    CAS  PubMed  Article  Google Scholar 

  39. Bonner JA, Harari PM, Giralt J et al (2006) Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med 354:567–578

    CAS  PubMed  Article  Google Scholar 

  40. Kosaka T, Yamaki E, Mogi A et al (2011) Mechanisms of resistance to EGFR TKIs and development of a new generation of drugs in non-small-cell lung cancer. J Biomed Biotechnol 2011:165214. doi:10.1155/2011/165214

    PubMed Central  PubMed  Article  Google Scholar 

  41. Zhang X, Chang A (2008) Molecular predictors of EGFR-TKI sensitivity in advanced non–small cell lung cancer. Int J Med Sci 5:209–217

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  42. Altieri DC (2001) The molecular basis and potential role of survivin in cancer diagnosis and therapy. Trends Mol Med 7:542–547

    CAS  PubMed  Article  Google Scholar 

  43. Span PN, Tjan-Heijnen VC, Manders P et al (2006) High survivin predicts a poor response to endocrine therapy, but a good response to chemotherapy in advanced breast cancer. Breast Cancer Res Treat 98:223–230

    CAS  PubMed  Article  Google Scholar 

  44. Wang Q, Greene MI (2005) EGFR enhances survivin expression through the phosphoinositide 3 (PI-3) kinase signaling pathway. Exp Mol Pathol 79:100–107

    CAS  PubMed  Article  Google Scholar 

  45. Xie D, Zeng YX, Wang HJ et al (2006) Expression of cytoplasmic and nuclear survivin in primary and secondary human glioblastoma. Br J Cancer 94:108–114

    CAS  PubMed Central  PubMed  Article  Google Scholar 

Download references

Acknowledgments

This experiment was finished in the Oncobiology Key Lab of Heilongjiang Common Institution of Higher Learning.

Conflict of interest

The authors have stated that they have no conflict of interest.

Author information

Affiliations

  1. Department of Medical Oncology, The Third Affiliated Hospital of Harbin Medical University, Road 150 of Nangang District, Harbin, Heilongjiang Province, 150081, China

    Minghui Zhang, Xiaosan Zhang, Shu Zhao, Yan Wang, Maopeng Yang & Qingyuan Zhang

  2. Department of Pathology, The First Affiliated Hospital of XinXiang Medical College, WeiHui, 454100, China

    Wenyu Di

  3. Department of Osteology, The 371 Hospital of the Chinese People’s Liberation Army, XinXiang, 453000, China

    Gangling Zhao

Authors
  1. Minghui Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xiaosan Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shu Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yan Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Wenyu Di
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Gangling Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Maopeng Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Qingyuan Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Qingyuan Zhang.

Additional information

M.H. Zhang, X.S. Zhang, and S. Zhao contributed equally to the work and should be considered as co-first authors.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Zhang, M., Zhang, X., Zhao, S. et al. Prognostic value of survivin and EGFR protein expression in triple-negative breast cancer (TNBC) patients. Targ Oncol 9, 349–357 (2014). https://doi.org/10.1007/s11523-013-0300-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11523-013-0300-y

Keywords

  • Triple-negative breast cancer
  • EGFR
  • Survivin
  • Prognosis