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

Jonine D. Figueroa, Kathleen C. Flanders, Montserrat Garcia-Closas, William F. Anderson, Xiaohong R. Yang, Rayna K. Matsuno, Máire A. Duggan, Ruth M. Pfeiffer, Akira Ooshima, Robert Cornelison, Gretchen L. Gierach, Louise A. Brinton, Jolanta Lissowska, Beata Peplonska, Lalage M. Wakefield, Mark E. Sherman

Research output: Contribution to journalArticlepeer-review

45 Scopus citations

Abstract

The transforming growth factor beta (TGF-β) pathway can play either a tumor-suppressing or a tumorpromoting 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-β2 (72%), and phospho-SMAD2 (61%), whereas intracellular-TGFβ1 was expressed in 32% of tumors. Expression of TGF-β ligands (β1, β2, and β3) was associated with prognosticaiIy 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 phosphoSMAD2 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.

Original languageEnglish (US)
Pages (from-to)727-735
Number of pages9
JournalBreast Cancer Research and Treatment
Volume121
Issue number3
DOIs
StatePublished - Jun 2010

Keywords

  • Breast cancer
  • Estrogen receptor
  • Transforming growth factor beta

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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