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Expression of TGF-β signaling factors in invasive breast cancers: relationships with age at diagnosis and tumor characteristics

  • Epidemiology
  • Published:
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Abstract

The transforming growth factor beta (TGF-β) pathway can play either a tumor-suppressing or a tumor-promoting role in human breast carcinogenesis. In order to determine whether expression of TGF-β signaling factors varies by age at onset and breast tumor characteristics that have prognostic significance, we undertook a study of 623 women with invasive breast carcinoma enrolled in a population-based case–control study conducted in Poland from 2000 to 2003. TGF-β signaling factors were analyzed by immunohistochemistry in tumor tissue microarrays. We found that most tumors expressed extracellular-TGF-β1 (78%), TGF-β2 (91%), TGF-β3 (93%), TGF-βR2 (72%), and phospho-SMAD2 (61%), whereas intracellular-TGF-β1 was expressed in 32% of tumors. Expression of TGF-β ligands (β1, β2, and β3) was associated with prognostically favorable pathological features including small size, and low grade, and these associations were similar for ER-positive and negative tumors. On the contrary, expression of the receptor TGF-βR2 was primarily associated with small tumor size among ER-negative tumors, while expression of the transcription factor phospho-SMAD2 was associated with positive nodal status among ER-negative tumors. The greater frequency of expression of phospho-SMAD2 in cancers associated with lymph node metastases is consistent with a pro-progression role for TGF-β. In addition, expression of extracellular-TGF-β1 (P = 0.005), TGF-βR2 (P = 8.2E-11), and phospho-SMAD2 (P = 1.3E-8) was strongly associated with earlier age at onset, independent of ER status. Our data provide evidence that TGF-β signaling patterns vary by age and pathologic features of prognostic significance including ER expression. These results warrant analysis in studies of clinical outcomes accounting for age, ER status and treatment.

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Authors and Affiliations

  1. Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

    Jonine D. Figueroa, Montserrat Garcia-Closas, William F. Anderson, Xiaohong R. Yang, Rayna K. Matsuno, Ruth M. Pfeiffer, Gretchen L. Gierach, Louise A. Brinton & Mark E. Sherman

  2. Laboratory of Cancer Biology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

    Kathleen C. Flanders, Akira Ooshima & Lalage M. Wakefield

  3. Departments of Pathology and Laboratory Medicine, University of Calgary, and Calgary Laboratory Services, Calgary, Canada

    Máire A. Duggan

  4. Genetics Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

    Robert Cornelison

  5. Department of Cancer Epidemiology and Prevention, M. Sklodowska-Curie Cancer Center and Institute of Oncology, Warsaw, Poland

    Jolanta Lissowska

  6. Department of Occupational and Environmental Epidemiology, Nofer Institute of Occupational Medicine, Lodz, Poland

    Beata Peplonska

Authors
  1. Jonine D. Figueroa
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  2. Kathleen C. Flanders
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  3. Montserrat Garcia-Closas
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  4. William F. Anderson
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  7. Máire A. Duggan
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  8. Ruth M. Pfeiffer
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  9. Akira Ooshima
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  10. Robert Cornelison
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  11. Gretchen L. Gierach
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  12. Louise A. Brinton
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  13. Jolanta Lissowska
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  14. Beata Peplonska
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  15. Lalage M. Wakefield
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  16. Mark E. Sherman
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Correspondence to Jonine D. Figueroa.

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Figueroa, J.D., Flanders, K.C., Garcia-Closas, M. et al. Expression of TGF-β signaling factors in invasive breast cancers: relationships with age at diagnosis and tumor characteristics. Breast Cancer Res Treat 121, 727–735 (2010). https://doi.org/10.1007/s10549-009-0590-z

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  • DOI: https://doi.org/10.1007/s10549-009-0590-z

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