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Alpha- and beta-adrenergic receptor (AR) protein expression is associated with poor clinical outcome in breast cancer: an immunohistochemical study

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Abstract

Breast cancer mortality is frequently associated with metastatic disease. Metastasis models have shown adrenoceptor (AR) stimulation induces cell migration which is inhibited by adrenoceptor antagonist drugs. We investigated adrenoceptor protein expression in clinical breast tumours and its association with disease progression and prognosis. Immunohistochemistry on tissue microarrays was used to characterise α1b, α2c and β22 adrenoceptor protein expression in operable breast tumours. Associations with tumour-relevant biological markers and clinical outcome were statistically assessed. Strong α1b expression occurred in large high grade (P < 0.0001), HER2+ (P < 0.0001) or basal-like (CK5/6, P = 0.0005; CK14, P = 0.0001; EGFR, P = 0.003) cancers, showing increased proliferation (Mib1, P = 0.002), decreased apoptosis (Bcl2, P < 0.0001) and poor NPI membership (P = 0.001). α1b expression correlated with poor cancer-specific survival (LR = 7.628, P = 0.022) and tumour recurrence (LR = 6.128, P = 0.047). Strong α2c was over-expressed in high grade (P = 0.007), HER3+ (P = 0.002) and HER4+ (P < 0.0001) cancers with borderline increase in EGFR, p53 and MIB1 proteins, and inverse association with hormonal (PgR, P = 0.002) phenotype. In contrast, strong β2 expression occurred in small-size, luminal-like (ER+, P < 0.001) tumours of low grade (P < 0.001) and lymph node stage (P = 0.027) that showed poor prognosis when hormonal treatment was withheld. Adrenoceptors were not found to be independent predictors of clinical outcome. Alpha1b and α2c AR is over-expressed in basal-like breast tumours of poor prognosis. Strong β2 adrenoceptor expression is seen in patients with a luminal (ER+) tumour phenotype and good prognosis, due to benefits derived from hormonal therapy. These findings suggest a possible role for targeted therapy using adrenoceptor antagonists.

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Abbreviations

AR:

Androgen receptor/adrenoceptor

BCSS:

Breast cancer-specific survival

CK:

Cytokeratin

DFI:

Disease-free interval

DM:

Distant metastasis

E:

Epinephrine

ER:

Oestrogen receptor

EGFR:

Epidermal growth factor receptor

NE:

Norepinephrine

PGR:

Progesterone receptor

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Acknowledgments

Members of the Institute of Immunology, Witten/Herdecke University were supported by the Fritz Bender Foundation (Munich, Germany). In addition, the ministry of higher education (Egypt) is thanked for funding HOH.

Conflict interests

The authors have no conflict of interests to declare

Author information

Authors and Affiliations

  1. Department of Cellular Pathology, Queen’s Medical Centre, Nottingham University Hospitals Trust and School of Molecular Medical Sciences, University of Nottingham, Nottingham, NG7 2UH, UK

    D. G. Powe, H. O. Habashy, A. R. Green & I. O. Ellis

  2. Institute of Immunology, University of Witten/Herdecke, 58448, Witten, Germany

    M. J. Voss, K. S. Zänker & F. Entschladen

Authors
  1. D. G. Powe
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  2. M. J. Voss
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  3. H. O. Habashy
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  4. K. S. Zänker
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  5. A. R. Green
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  6. I. O. Ellis
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  7. F. Entschladen
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Corresponding author

Correspondence to D. G. Powe.

Electronic supplementary material

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Table 1

Supplementary material 1 (DOC 45 kb)

Table 2

Characteristics for patients investigated for α1b adrenoceptor protein expression (DOC 90 kb)

Table 3

Associations between α1b adrenoceptor protein expression and tumour relevant markers (DOC 122 kb)

Table 4

Characteristics for patients investigated for α2c adrenoceptor protein expression (DOC 90 kb)

Table 5

Associations between α2c adrenoceptor protein expression and tumour relevant markers (DOC 121 kb)

Table 6

Characteristics for patients investigated for β2 adrenoceptor protein expression (DOC 90 kb)

Table 7

Associations between β2 adrenoceptor protein expression and tumour relevant markers (DOC 122 kb)

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Powe, D.G., Voss, M.J., Habashy, H.O. et al. Alpha- and beta-adrenergic receptor (AR) protein expression is associated with poor clinical outcome in breast cancer: an immunohistochemical study. Breast Cancer Res Treat 130, 457–463 (2011). https://doi.org/10.1007/s10549-011-1371-z

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  • DOI: https://doi.org/10.1007/s10549-011-1371-z

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