TY - JOUR
T1 - Expression of TGF-β signaling factors in invasive breast cancers
T2 - Relationships with age at diagnosis and tumor characteristics
AU - Figueroa, Jonine D.
AU - Flanders, Kathleen C.
AU - Garcia-Closas, Montserrat
AU - Anderson, William F.
AU - Yang, Xiaohong R.
AU - Matsuno, Rayna K.
AU - Duggan, Máire A.
AU - Pfeiffer, Ruth M.
AU - Ooshima, Akira
AU - Cornelison, Robert
AU - Gierach, Gretchen L.
AU - Brinton, Louise A.
AU - Lissowska, Jolanta
AU - Peplonska, Beata
AU - Wakefield, Lalage M.
AU - Sherman, Mark E.
PY - 2010/6
Y1 - 2010/6
N2 - 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.
AB - 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.
KW - Breast cancer
KW - Estrogen receptor
KW - Transforming growth factor beta
UR - http://www.scopus.com/inward/record.url?scp=77953120606&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77953120606&partnerID=8YFLogxK
U2 - 10.1007/s10549-009-0590-z
DO - 10.1007/s10549-009-0590-z
M3 - Article
C2 - 19937272
AN - SCOPUS:77953120606
SN - 0167-6806
VL - 121
SP - 727
EP - 735
JO - Breast Cancer Research and Treatment
JF - Breast Cancer Research and Treatment
IS - 3
ER -