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

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


Mohammed A. Aleskandarany

Devika Agarwal

Assistant Professor

Graham Ball

Ahmed Elmouna

Ibraheem Ashankyty

Edem Nuglozeh

Mohammad F. Fazaludeen

Maria Diez-Rodriguez

Christopher C. Nolan

Professor of Molecular Immunology

Professor of Breast Cancer Pathology


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.

Journal Article Type Article
Acceptance Date Feb 6, 2016
Online Publication Date Feb 23, 2016
Publication Date Feb 23, 2016
Deposit Date Oct 16, 2018
Journal Breast Cancer Research and Treatment
Print ISSN 0167-6806
Electronic ISSN 1573-7217
Publisher Springer Verlag
Peer Reviewed Peer Reviewed
Volume 156
Issue 1
Pages 9-20
Public URL
Publisher URL