Breast Cancer Research and Treatment

, Volume 156, Issue 1, pp 9–20 | Cite as

The prognostic significance of STAT3 in invasive breast cancer: analysis of protein and mRNA expressions in large cohorts

  • Mohammed A. Aleskandarany
  • Devika Agarwal
  • Ola H. Negm
  • Graham Ball
  • Ahmed Elmouna
  • Ibraheem Ashankyty
  • Edem Nuglozeh
  • Mohammad F. Fazaludeen
  • Maria Diez-Rodriguez
  • Christopher C. Nolan
  • Patrick J. Tighe
  • Andrew R. Green
  • Ian O. Ellis
  • Emad A. Rakha
Preclinical study


Signal transducer and activator of transcription (STAT) transcription factors family are involved in diverse cellular biological functions. Reports regarding the prognostic impact of STAT3 expression in breast cancer (BC) are variable whether being a factor of poor or good prognosis. Immunohistochemical expression of phospho-STAT3 (pSTAT3) was studied in large series of invasive BC (n = 1270). pSTAT3 and STAT3 were quantified using reverse phase protein array (RPPA) on proteins extracted from macro-dissected FFPE tissues (n = 49 cases). STAT3 gene expression in the METABRIC cohort was also investigated. STAT3 gene expression prognostic impact was externally validated using the online BC gene expression data (n = 26 datasets, 4.177 patients). pSTAT3 was expressed in the nuclei and cytoplasm of invasive BC cells. Nuclear pSTAT3 overexpression was positively associated with smaller tumour size, lower grade, good NPI, negative lymphovascular invasion (LVI), ER+, PgR+, p53−, HER2−, and low Ki67LI and an improved breast cancer-specific survival (BCSS), independently of other factors. On RPPA, the mean pSTAT3 and STAT3 expressions were higher in ER+, PgR+, and smaller size tumours. Higher STAT3 transcripts in the METABRIC cohort were observed in cases with favourable prognostic criteria and as well as improved BCSS within the whole cohort, ER+ cohort with and without hormonal therapy, and ER− cohort including those who did not receive adjuvant chemotherapy. Pooled STAT3 gene expression data in the external validation cohort showed an association with improved patients’ outcome (P < 0.001, HR = 0.84, 95 % CI 0.79–0.90). Results of this study suggest nuclear localisation of pSTAT3 as favourable prognostic marker in invasive BC, results re-enforced by analysis of STAT3 gene expression data. This good prognostic advantage was maintained in patients who received and who did not receive adjuvant therapy. Therefore, STAT3 could have context-dependent molecular roles of in BC, results which warrant further prospective verification in clinical trials.


STAT3 Breast cancer Reverse phase protein array RPPA METABRIC 


Compliance with ethical standards

Conflict of interest

All the authors have no conflicts of interest to declare.

Supplementary material

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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Mohammed A. Aleskandarany
    • 1
    • 2
  • Devika Agarwal
    • 3
  • Ola H. Negm
    • 4
  • Graham Ball
    • 3
  • Ahmed Elmouna
    • 5
  • Ibraheem Ashankyty
    • 5
  • Edem Nuglozeh
    • 5
  • Mohammad F. Fazaludeen
    • 5
  • Maria Diez-Rodriguez
    • 1
  • Christopher C. Nolan
    • 1
  • Patrick J. Tighe
    • 4
  • Andrew R. Green
    • 1
  • Ian O. Ellis
    • 1
  • Emad A. Rakha
    • 1
    • 2
  1. 1.Division of Cancer and Stem Cells, School of MedicineUniversity of Nottingham and Nottingham University Hospitals NHS TrustNottinghamUK
  2. 2.Department of Pathology, Faculty of MedicineMenoufia UniversityMenoufiaEgypt
  3. 3.School of Science & TechnologyNottingham Trent UniversityNottinghamUK
  4. 4.Division of ImmunologySchool of Medicine, University of NottinghamNottinghamUK
  5. 5.Molecular Diagnostics and Personalised Therapeutics UnitUniversity of Ha’ilHa’ilSaudi Arabia

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