A phenotype from tumor stroma based on the expression of metalloproteases and their inhibitors, associated with prognosis in breast cancer
A phenotype from tumor stroma based on the expression of metalloproteases and their inhibitors, associated with prognosis in breast cancer
复制标题
DOI：
10.4161/2162402x.2014.992222
复制
发表时间：
2015-01-01
期刊：
影响因子：
7.2
通讯作者：
Vizoso, Francisco J.
中科院分区：
文献类型：
--
作者：
Eiro, Noem;Fernandez-Garcia, Belen;Vizoso, Francisco J.
本研究的目的是评估早期乳腺癌患者中单核炎性细胞(MICs)和肿瘤相关成纤维细胞(CAF)的表型的影响，特别是它们的表达与其在肿瘤中的位置(即位于肿瘤中心或侵袭性前沿)和远处转移的发生有关。应用免疫组织化学方法和免疫组织化学方法，对107例乳腺导管浸润性肿瘤患者肿瘤中心和肿瘤侵袭前沿的基质金属蛋白酶-1、-2、-7、-9、-11、-13和-14及其抑制物-1、-2和-3进行了免疫组织化学研究。数据分析采用非监督层次聚类分析。我们的结果表明，无论是在肿瘤中心还是在肿瘤侵袭前沿，MICs中的MICs和CAF中的TIMP-2的表达是预测患者临床预后的最有效的独立预后因素。使用无监督的等级聚类分析，我们发现明确的病例聚类识别肿瘤亚群，显示基质细胞(CAF和MICs)在肿瘤中心和侵袭前沿的高分子水平表达MMPs/TIMPs，这与较高的远处转移发生率密切相关。此外，我们发现定义乳腺癌亚群的这些簇的组合在临床结果上有很大的不同。本文提出的结果确定了有助于根据肿瘤间质将患者分成不同亚组的生物标志物，这可能有助于更好地了解乳腺癌患者的预后。
The objective of the present work was to evaluate the impact of the phenotype of both mononuclear inflammatory cells (MICs) and cancer-associated fibroblast (CAFs) in early breast cancer patients, specifically assessed as to their expression of MMP/TIMP relative to their position within the tumor (i.e., localization at the tumor center or invasive front) and the occurrence of distant metastases.. An immunohistochemical study was performed using tissue arrays and specific antibodies against matrix metalloproteinase (MMP)-1, -2, -7, -9, -11, -13 and -14, tissue inhibitors of metalloproteinase (TIMP)-1, -2 and -3, both at tumor center and at invasive front, in 107 patients with primary ductal invasive breast tumors. Data were analyzed by unsupervised hierarchical clustering analysis. Our results indicated that MMP-11 expression by MICs, and TIMP-2 expression by CAFs at either the tumor center or the invasive front, were the most potent independent prognostic factors for predicting the clinical outcome of patients. Using the unsupervised hierarchical clustering analysis, we found well-defined clusters of cases identifying subgroups of tumors showing a high molecular profile of MMPs/TIMPs expression by stromal cells (CAFs and MICs), both at the tumor center and at the invasive front, which were strongly associated with a higher prevalence of distant metastasis. In addition, we found combinations of these clusters defining subpopulations of breast carcinomas differing widely in their clinical outcome. The results presented here identify biologic markers useful to categorize patients into different subgroups based on their tumor stroma, which may contribute to improved understanding of the prognosis of breast cancer patients.