title: The relationship between total and phosphorylated STAT1 and STAT3 tumour cell expression, components of tumour microenvironment and survival in patients with invasive ductal breast cancer.
abstract: The aim of the present study was to examine the relationship between tumour cell expression of total and phosphorylated STAT1 (ph-STAT1) and STAT3 (ph-STAT-3), components of tumour microenvironment and survival in patients with invasive ductal breast cancer.Immunohistochemical analysis of total and ph-STAT1, and STAT3 were performed on tissue microarray of 384 breast cancer specimens. Tumour cell expression of STAT1 and STAT3 at both cytoplasmic and nuclear locations were combined and identified as STAT1/STAT3 tumour cell expression. These results were related to cancer specific survival (CSS) and phenotypic features of the tumour and the host.High ph-STAT1 and ph-STAT3 tumour cell expression were associated with increased ER (both P≤0.001) and PR (both P <0.05), reduced tumour grade (P=0.015 and P<0.001 respectively) and necrosis (both P=0.001). Ph-STAT1 was associated with increased general inflammatory infiltrate (P=0.007) and ph-STAT3 was associated with lower CD4+ infiltration (P=0.024). In multivariate survival analysis, only high ph-STAT3 tumour cell expression was a predictor of improved CSS (P=0.010) independent of other tumour and host-based factors.STAT1 and STAT3 tumour cell expression appeared to be an important determinant of favourable outcome in patients with invasive ductal breast cancer. The present results suggest that STAT1 and STAT3 may affect disease outcome through direct impact on tumour cells, counteracting aggressive tumour features, as well as interaction with the surrounding microenvironment.
authors: Academic Unit of Surgery, College of Medical, Veterinary and Life Sciences-University of Glasgow, Royal Infirmary, Glasgow, Scotland.|Unit of Experimental Therapeutics, Institute of Cancer, College of Medical, Veterinary and Life Sciences-University of Glasgow, Wolfson Wohl Cancer Research Centre, Glasgow, Scotland.
authors: Fadia J A
authors: FJ
authors: Gujam
authors: Academic Unit of Surgery, College of Medical, Veterinary and Life Sciences-University of Glasgow, Royal Infirmary, Glasgow, Scotland.
authors: Donald C
authors: DC
authors: McMillan
authors: Unit of Experimental Therapeutics, Institute of Cancer, College of Medical, Veterinary and Life Sciences-University of Glasgow, Wolfson Wohl Cancer Research Centre, Glasgow, Scotland.
authors: Joanne
authors: J
authors: Edwards
mesh_terms: D000328:Adult; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism / Q000473:pathology*; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D005260:Female; D006801:Humans; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D010766:Phosphorylation; D050794:STAT1 Transcription Factor / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D016019:Survival Analysis; D046888:Tissue Array Analysis; D059016:Tumor Microenvironment
chemical_list: D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human
keywords: STAT1; STAT3; breast cancer; tumour microenvironment and survival