Clinical and Translational Oncology

, Volume 14, Issue 3, pp 232–236 | Cite as

Tissue microarray-based study of patients with lymph node-positive breast cancer shows tyrosine phosphorylation of signal transducer and activator of transcription 3 (tyrosine705-STAT3) is a marker of good prognosis

  • Amir Sonnenblick
  • Anat Shriki
  • Eithan Galun
  • Jonathan H. Axelrod
  • Hagit Daum
  • Yakir Rottenberg
  • Tamar Hamburger
  • Bela Mali
  • Tamar Peretz
Research Articles



Although lymph node-positive breast cancers are associated with poorer prognosis, individual patients may have different clinical outcomes. Signal transducer and activator of transcription 3 (STAT3) is a point of convergence for numerous oncogenic signalling pathways. The goal of this study was to determine the prognostic value of phosphorylated (tyrosine705)-STAT3 in node-positive breast cancer patients.


Immunohistochemical analysis of Phospho-STAT3 was performed on a tissue microarray of breast cancer specimens. The expression pattern of Phospho-STAT3 was correlated with survival outcome, and clinical and pathological parameters.


Out of 125 interpretable tumours, positive Phospho-STAT3 nuclear expression was seen in 35 (28%) of tumours. There was no significant relationship between Phospho-STAT3 expression and clinical-pathological parameters including age, hormonal receptor status, grade and tumour size. Interestingly positive tumours had a significantly improved disease-free survival at 5 years (p=0.035). Additionally, positive Phospho-STAT3 nuclear expression was correlated with significantly improved survival at both 5 years (p=0.023) and 10 years (p=0.026). Finally, in multivariate analyses Phospho-STAT3 was found to be an independent prognostic marker of overall survival in node-positive breast cancer patients.


These findings support the role of Phospho-STAT3 as an important independent prognostic marker in node-positive breast cancer patients.


Breast cancer Phosphorylation STAT3 Tissue microarray Immunohistochemistry 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Paik S, Shak S, Tang G et al (2004) A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med 351:2817–2826PubMedCrossRefGoogle Scholar
  2. 2.
    Goldstein LJ, Gray R, Badve S et al (2008) Prognostic utility of the 21-gene assay in hormone receptor-positive operable breast cancer compared with classical clinicopathologic features. J Clin Oncol 26:4063–4071PubMedCrossRefGoogle Scholar
  3. 3.
    Levy DE, Lee CK (2002) What does Stat3 do? J Clin Invest 109:1143–1148PubMedGoogle Scholar
  4. 4.
    Calo V, Migliavacca M, Bazan V et al (2003) STAT proteins: from normal control of cellular events to tumorigenesis. J Cell Physiol 197:157–168PubMedCrossRefGoogle Scholar
  5. 5.
    Sonnenblick A, Levy C, Razin E (2004) Interplay between MITF, PIAS3, and STAT3 in mast cells and melanocytes. Mol Cell Biol 24:10584–10592PubMedCrossRefGoogle Scholar
  6. 6.
    Hodge DR, Hurt EM, Farrar WL (2005) The role of IL-6 and STAT3 in inflammation and cancer. Eur J Cancer 41:2502–2512PubMedCrossRefGoogle Scholar
  7. 7.
    Yoshimura A (2006) Signal transduction of inflammatory cytokines and tumor development. Cancer Sci 97:439–447PubMedCrossRefGoogle Scholar
  8. 8.
    Watson CJ, Miller WR (1995) Elevated levels of members of the STAT family of transcription factors in breast carcinoma nuclear extracts. Br J Cancer 71:840–844PubMedCrossRefGoogle Scholar
  9. 9.
    Perou CM, Jeffrey SS, van de Rijn M et al (1999) Distinctive gene expression patterns in human mammary epithelial cells and breast cancers. Proc Natl Acad Sci U S A 96:9212–9217PubMedCrossRefGoogle Scholar
  10. 10.
    Berclaz G, Altermatt HJ, Rohrbach V et al (2001) EGFR dependent expression of STAT3 (but not STAT1) in breast cancer. Int J Oncol 19:1155–1160PubMedGoogle Scholar
  11. 11.
    Kononen J, Bubendorf L, Kallioniemi A et al (1998) Tissue microarrays for high-throughput molecular profiling of tumor specimens. Nat Med 4:844–847PubMedCrossRefGoogle Scholar
  12. 12.
    Nechemia-Arbely Y, Barkan D, Pizov G et al (2008) IL-6/IL-6R axis plays a critical role in acute kidney injury. J Am Soc Nephrol 19:1106–1115PubMedCrossRefGoogle Scholar
  13. 13.
    Dolled-Filhart M, Camp RL, Kowalski DP et al (2003) Tissue microarray analysis of signal transducers and activators of transcription 3 (Stat3) and phospho-Stat3 (Tyr705) in node-negative breast cancer shows nuclear localization is associated with a better prognosis. Clin Cancer Res 9:594–600PubMedGoogle Scholar
  14. 14.
    McShane LM, Altman DG, Sauerbrei W et al (2006) REporting recommendations for tumor MARKer prognostic studies (REMARK). Breast Cancer Res Treat 100:229–235PubMedCrossRefGoogle Scholar
  15. 15.
    Barbieri I, Pensa S, Pannellini T et al (2010) Constitutively active Stat3 enhances neu-mediated migration and metastasis in mammary tumors via upregulation of Cten. Cancer Res 70:2558–2567PubMedCrossRefGoogle Scholar
  16. 16.
    Barbieri I, Quaglino E, Maritano D et al (2010) Stat3 is required for anchorage-independent growth and metastasis but not for mammary tumor development downstream of the ErbB-2 oncogene. Mol Carcinog 49:114–120PubMedGoogle Scholar
  17. 17.
    Dien J, Amin HM, Chiu N et al (2006) Signal transducers and activators of transcription-3 upregulates tissue inhibitor of metalloproteinase-1 expression and decreases invasiveness of breast cancer. Am J Pathol 169:633–642PubMedCrossRefGoogle Scholar
  18. 18.
    Chapman RS, Lourenco PC, Tonner E et al (1999) Suppression of epithelial apoptosis and delayed mammary gland involution in mice with a conditional knockout of Stat3. Genes Dev 13:2604–2616PubMedCrossRefGoogle Scholar
  19. 19.
    Sutherland KD, Vaillant F, Alexander WS et al (2006) c-myc as a mediator of accelerated apoptosis and involution in mammary glands lacking Socs3. EMBO J 25:5805–5815PubMedCrossRefGoogle Scholar
  20. 20.
    Sarosiek KA, Malumbres R, Nechushtan H et al (2010) Novel IL-21 signaling pathway upregulates c-Myc and induces apoptosis of diffuse large B-cell lymphomas. Blood 115:570–580PubMedCrossRefGoogle Scholar
  21. 21.
    Real PJ, Sierra A, De Juan A et al (2002) Resistance to chemotherapy via Stat3-dependent overexpression of Bcl-2 in metastatic breast cancer cells. Oncogene 21:7611–7618PubMedCrossRefGoogle Scholar

Copyright information

© Feseo 2012

Authors and Affiliations

  • Amir Sonnenblick
    • 1
    • 2
  • Anat Shriki
    • 2
  • Eithan Galun
    • 2
  • Jonathan H. Axelrod
    • 2
  • Hagit Daum
    • 3
  • Yakir Rottenberg
    • 1
  • Tamar Hamburger
    • 1
  • Bela Mali
    • 4
  • Tamar Peretz
    • 1
  1. 1.Sharett Institute of OncologyHadassah-Hebrew University Medical CenterJerusalemIsrael
  2. 2.Goldyne Savad Institute of Gene TherapyHadassah-Hebrew University Medical CenterJerusalemIsrael
  3. 3.Department of Obstetrics and GynecologyHadassah-Hebrew University Medical CenterMt Scopus, JerusalemIsrael
  4. 4.Department of PathologyHadassah-Hebrew University HospitalJerusalemIsrael

Personalised recommendations