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Characterization of type III TGF-β receptor expression in invasive breast carcinomas: a potential new marker and target for triple negative breast cancer

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Journal of Cell Communication and Signaling Aims and scope

Abstract

Invasive breast carcinomas are heterogeneous and exhibit distinct molecular features and biological behavior. Understanding the underlying molecular events that promote breast cancer progression is necessary to improve treatment and prognostication. TGF-β receptor III (TBR3) is a member of the TGF-β signaling pathway, with functions in cell proliferation and migration in malignancies, including breast cancer. Recent studies propose that TBR3 may function as a tumor suppressor and that its loss may correlate with disease progression. However, there are limited data on the expression of TBR3 in breast cancer in relationship to tumor type, hormonal receptor status and HER-2/neu, and patient outcome. In this study, we investigated the expression of TBR3 in a cohort of 205 primary invasive breast carcinomas in tissue microarrays (TMAs), with comprehensive clinical, pathological and follow- up information. Sections were stained for TBR3 and evaluated for intensity of reactivity based on a 4-tiered scoring system (1 to 4; TBR3 low = scores 1–2; TBR3 high = scores 3–4). Of the 205 invasive carcinomas, 123 were luminal type (95 type A, 28 type B), 8 were HER-2 type, and 62 were triple negative (TN). TBR3 was high in 112 (55 %) and low in 93 (45 %) cases. Low TBR3 was associated with higher histological grade and worse disease free and overall survival, all features of biologically aggressive breast carcinomas. TBR3 was significantly associated with the subtype of breast cancer, as low TBR3 was detected in 95 % of TN compared to 22 % of luminal tumors (p < 0.0001). We discovered a significant association between low TBR3 protein expression, TN breast cancer phenotype, and disease progression. These data suggest that TBR3 loss might be linked to the development of TN breast cancers and pave the way to investigating whether restoring TBR3 function may be a therapeutic strategy against TN breast carcinomas.

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Acknowledgments

This work was supported by NIH grants R01 CA107469, R01 CA125577 and U01CA154224 (to CGK), the University of Michigan’s Cancer Center Support Grant (5 P30 CA46592).

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Authors and Affiliations

  1. Department of Pathology, University of Michigan Medical School, 4217 Comprehensive Cancer Center, 1500 E. Medical Center Dr., Ann Arbor, MI, 48109, USA

    Judy C. Pang, Nilam K. Virani & Celina G. Kleer

  2. Biostatistics, University of Michigan Medical School, Ann Arbor, MI, 48109, USA

    Kelley M. Kidwell

  3. Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI, 48109, USA

    Celina G. Kleer

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  1. Judy C. Pang
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  2. Nilam K. Virani
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  3. Kelley M. Kidwell
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  4. Celina G. Kleer
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Correspondence to Celina G. Kleer.

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Pang, J.C., Virani, N.K., Kidwell, K.M. et al. Characterization of type III TGF-β receptor expression in invasive breast carcinomas: a potential new marker and target for triple negative breast cancer. J. Cell Commun. Signal. 8, 211–218 (2014). https://doi.org/10.1007/s12079-014-0240-z

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  • DOI: https://doi.org/10.1007/s12079-014-0240-z

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