Expression of TGF-beta signaling factors in invasive breast cancers: relationships with age at diagnosis and tumor characteristics.
Expression of TGF-beta signaling factors in invasive breast cancers: relationships with age at diagnosis and tumor characteristics.
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DOI：
10.1007/s10549-009-0590-z
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发表时间：
2010-06
影响因子：
3.8
通讯作者：
Sherman ME
中科院分区：
文献类型：
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作者：
Figueroa JD;Flanders KC;Garcia-Closas M;Anderson WF;Yang XR;Matsuno RK;Duggan MA;Pfeiffer RM;Ooshima A;Cornelison R;Gierach GL;Brinton LA;Lissowska J;Peplonska B;Wakefield LM;Sherman ME
转化生长因子β（transforming growth factor beta，TGF-β）通路在乳腺癌的发生发展中具有抑瘤或促瘤作用。为了确定TGF-β信号传导因子的表达是否因发病年龄和具有预后意义的乳腺肿瘤特征而异，我们对2000年至2003年在波兰进行的一项基于人群的病例对照研究中纳入的623名浸润性乳腺癌妇女进行了研究。通过免疫组织化学在肿瘤组织芯片中分析TGF-β信号传导因子。我们发现大多数肿瘤表达细胞外TGF-β1（78%）、TGF-β2（91%）、TGF-β3（93%）、TGF-βR2（72%）和磷酸化SMAD 2（61%），而细胞内TGF-β1在32%的肿瘤中表达。TGF-β配体（β1、β2和β3）的表达与良性肿瘤的病理特征（包括小肿瘤和低级别）相关，这些相关性与ER阳性和阴性肿瘤相似。相反，受体TGF-βR2的表达主要与ER阴性肿瘤中的小肿瘤大小相关，而转录因子phospho-SMAD 2的表达与ER阴性肿瘤中的阳性淋巴结状态相关。在与淋巴结转移相关的癌症中，磷酸化SMAD 2的表达频率更高，这与TGF-β的促进展作用一致。此外，细胞外TGF-β1（P = 0.005）、TGF-βR2（P = 8.2E-11）和磷酸化SMAD 2（P = 1.3E-8）的表达与发病年龄较早密切相关，与ER状态无关。我们的数据提供的证据表明，TGF-β信号模式不同的年龄和病理特征的预后意义，包括ER表达。这些结果保证了在考虑年龄、ER状态和治疗的临床结局研究中的分析。
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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影响因子：
3.8
作者：
Yang, Xiaohong R.;Sherman, Mark E.;Garcia-Closas, Montserrat
通讯作者：
Garcia-Closas, Montserrat
影响因子：
5
作者：
DEVESA, SS;DONALDSON, J;FEARS, T
通讯作者：
FEARS, T
影响因子：
8.8
作者：
Mu, L.;Katsaros, D.;Lu, L.;Preti, M.;Durando, A.;Arisio, R.;Yu, H.
通讯作者：
Yu, H.
影响因子：
10.3
作者：
Anderson, William F.;Rosenberg, Philip S.;Pfeiffer, Ruth M.
通讯作者：
Pfeiffer, Ruth M.
影响因子：
8.8
作者：
通讯作者：
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