Details

Autor(en) / Beteiligte

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

Titel

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

Ist Teil von

• Breast cancer research and treatment, 2010-06, Vol.121 (3), p.727

Ort / Verlag

Dordrecht: Springer

Erscheinungsjahr

2010

Link zum Volltext

Quelle

SpringerLink

Beschreibungen/Notizen

• The transforming growth factor beta (TGF-[beta]) pathway can play either a tumor-suppressing or a tumor-promoting role in human breast carcinogenesis. In order to determine whether expression of TGF-[beta] 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-[beta] signaling factors were analyzed by immunohistochemistry in tumor tissue microarrays. We found that most tumors expressed extracellular-TGF-[[beta].sub.1] (78%), TGF-[[beta].sub.2] (91%), TGF-[[beta].sub.3] (93%), TGF-[beta]R2 (72%), and phospho-SMAD2 (61%), whereas intracellular-TGF-[[beta].sub.1] was expressed in 32% of tumors. Expression of TGF-[beta] ligands [[beta].sub.2], and [[beta].sub.3]) 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-[beta]R2 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-[beta].In addition, expression of extracellular-TGF-[beta]1(P = 0.005), TGF-[beta]R2 (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-[beta] 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. Keywords Transforming growth factor beta * Breast cancer * Estrogen receptor