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. 2016 Nov 22;7(47):77607-77621.
doi: 10.18632/oncotarget.12730.

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

Fadia J A Gujam  1   2 , Donald C McMillan  1 , Joanne Edwards  2
Affiliations

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

Fadia J A Gujam et al. Oncotarget. .

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.

Keywords: STAT1; STAT3; breast cancer; tumour microenvironment and survival.

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Conflict of interest statement

CONFLICTS OF INTEREST

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1. Sections of invasive ductal beast carcinomas showing IHC expression levels of ph-STAT1 (first row) and ph-STAT3 (second row)
No appreciable expression was detected in the negative controls of ph-STAT1 A. and ph-STAT3 B. C-H. show the staining intensity of the STAT1 and STAT3 expression as low (C and D), moderate (E and F), and strong (G and H). Original magnification, 20×. Scale bars = 100 μm (A-F), 10 μm (G and H).
Figure 2
Figure 2. Kaplan-Meier survival curves (Log rank) of cancer specific survival
A. Total STAT1 tumour cell expression and B. Ph-STAT1 tumour cell expression. C. Total STAT3 tumour cell expression and D. Ph-STAT3 tumour cell expression.
Figure 3
Figure 3. Kaplan-Meier survival curves (Log rank) of ph-STAT1 in different molecular subtypes
Only Luminal A (n=174, 45%) shows significant association between high tumour cell expression of ph-STAT1 (n=121, 32%) and improved cancer specific survival
Figure 4
Figure 4. Kaplan-Meier survival curves (Log rank) of ph-STAT3 in different molecular subtypes
Luminal A (n=174, 45%) and luminal B (n=92, 24%) show significant association between high tumour cell expression of ph-STAT3 (n=109, 28%) and improved cancer specific survival. Manipulation is permitted.
See this image and copyright information in PMC

References

    1. Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Bray F. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN2012. International journal of cancer. 2015;5:E359–86. - PubMed
    1. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144:646–674. - PubMed
    1. McAllister SS, Weinberg RA. The tumour-induced systemic environment as a critical regulator of cancer progression and metastasis. Nat Cell Biol. 2014;16:717–27. - PMC - PubMed
    1. Schindler C, Levy DE, Decker T. JAK-STAT signaling: from interferons to cytokines. J Biol Chem. 2007;282:20059–63. - PubMed
    1. Stark GR, Darnell JE., Jr The JAK-STAT pathway at twenty. Immunity. 2012;36:503–14. - PMC - PubMed