Analysis of stromal signatures in the tumor microenvironment of ductal carcinoma in situ.
Analysis of stromal signatures in the tumor microenvironment of ductal carcinoma in situ.
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DOI：
10.1007/s10549-009-0654-0
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发表时间：
2010-09
影响因子：
3.8
通讯作者：
West, R. B.
中科院分区：
文献类型：
--
作者：
Sharma, M.;Beck, A. H.;Webster, J. A.;Espinosa, I.;Montgomery, K.;Varma, S.;van de Rijn, M.;Jensen, K. C.;West, R. B.
肿瘤微环境研究的最新进展揭示了模型系统中肿瘤细胞与其周围间质之间的显著相互作用。我们先前已经证明，来自巨噬细胞(CSF1)反应和成纤维细胞(DTF样)反应的两种不同的间质信号存在于浸润性乳腺癌的亚型中，并与临床结果相关。在本研究中，我们探讨这些信号是否也存在于导管原位癌(DCIS)的间质中。我们通过公开的DCIS数据集的基因表达谱分析和免疫组织化学(IHC)对DCIS和浸润性乳腺癌病例的组织微阵列的特征进行了研究。基因表达和免疫组织化学数据均显示巨噬细胞反应和成纤维细胞表达特征存在于DCIS亚型的间质中。间质征象在DCIS中的发生率与我们先前报道的浸润性乳腺癌的发生率相似。我们还发现巨噬细胞反应特征与较高级别的DCIS和ER和PR阴性的病例有关，而成纤维细胞的特征与DCIS的任何临床病理特征无关。比较115例DCIS和浸润性乳腺癌的匹配病例，发现DCIS的间质反应类型与同一患者的浸润性导管癌(IDC)的巨噬细胞反应和成纤维细胞间质特征之间存在相关性(分别为P=0.03和0.08)。这项研究是首次在DCIS中对这些签名进行表征。这些征象具有显著的临床病理相关性，并且随着肿瘤从DCIS进展到浸润性乳腺癌而趋于保守。
Recent advances in the study of the tumor microenvironment have revealed significant interaction between tumor cells and their surrounding stroma in model systems. We have previously shown that two distinct stromal signatures derived from a macrophage (CSF1) response and a fibroblastic (DTF-like) response are present in subsets of invasive breast cancers and show a correlation with clinical outcome. In the present study we explore whether these signatures also exist in the stroma of ductal carcinoma in situ (DCIS). We studied the signatures by both gene expression profile analysis of a publically available data set of DCIS and by immunohistochemistry (IHC) on a tissue microarray of DCIS and invasive breast cancer cases. Both the gene expression and immunohistochemical data show that the macrophage response and fibroblast expression signatures are present in the stroma of subsets of DCIS cases. The incidence of the stromal signatures in DCIS is similar to the incidence in invasive breast cancer that we have previously reported. We also find that the macrophage response signature is associated with higher grade DCIS and cases which are ER and PR negative, whereas the fibroblast signature was not associated with any clinicopathologic features in DCIS. A comparison of 115 matched cases of DCIS and invasive breast cancer found a correlation between the type of stromal response in DCIS and invasive ductal carcinoma (IDC) within the same patient for both the macrophage response and the fibroblast stromal signatures (P = 0.03 and 0.08, respectively). This study is a first characterization of these signatures in DCIS. These signatures have significant clinicopathologic associations and tend to be conserved as the tumor progresses from DCIS to invasive breast cancer.
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DOI：
10.1158/1078-0432.ccr-08-1283
发表时间：
2009-02-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Beck AH;Espinosa I;Edris B;Li R;Montgomery K;Zhu S;Varma S;Marinelli RJ;van de Rijn M;West RB
通讯作者：
West RB
DOI：
10.1186/bcr1666
发表时间：
2007
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Vincent-Salomon A;Gruel N;Lucchesi C;MacGrogan G;Dendale R;Sigal-Zafrani B;Longy M;Raynal V;Pierron G;de Mascarel I;Taris C;Stoppa-Lyonnet D;Pierga JY;Salmon R;Sastre-Garau X;Fourquet A;Delattre O;de Cremoux P;Aurias A
通讯作者：
Aurias A
影响因子：
5
作者：
Beck, Andrew H.;Espinosa, Inigo;West, Robert B.
通讯作者：
West, Robert B.
影响因子：
3.6
作者：
Shekhar, Malathy P. V.;Tait, Larri;Miller, Fred R.
通讯作者：
Miller, Fred R.
影响因子：
3.8
作者：
Pavlakis, Kitty;Messini, Irene;Stathopoulos, Efstathios N.
通讯作者：
Stathopoulos, Efstathios N.