Prognostic Significance of Epithelial-Mesenchymal and Mesenchymal-Epithelial Transition Protein Expression in Non-Small Cell Lung Cancer
Prognostic Significance of Epithelial-Mesenchymal and Mesenchymal-Epithelial Transition Protein Expression in Non-Small Cell Lung Cancer
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DOI：
10.1158/1078-0432.ccr-08-0935
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发表时间：
2008-11-15
影响因子：
11.5
通讯作者：
Kristiansen, Glen
中科院分区：
文献类型：
--
作者：
Soltermann, Alex;Tischler, Verena;Kristiansen, Glen
目的：在肿瘤中，浸润性肿瘤的生长伴随着间质增生反应，并由癌细胞的上皮-间质转化（EMT）促进。我们研究了EMT指示蛋白periostin和vimentin与versican的预后意义，versican被认为是间充质-上皮转化（MET）的相反机制的指示蛋白，以及非小细胞肺癌（NSCLC）的结缔组织形成蛋白胶原和弹性蛋白。实验设计：采用免疫组化（EMT-MET蛋白）和Elastica van Gieson组织化学染色（胶原蛋白和弹性蛋白）分析533例手术切除的非小细胞肺癌患者的肿瘤间质和上皮蛋白表达。在三个组织微阵列上进行了半定量和评分系统。结果：533例患者中，48%为鳞状细胞癌，47%为腺癌，5%为腺鳞癌。骨膜素在间质或肿瘤上皮中的高表达，由两名病理学家独立评分，与男性、高分期、高pT分类和较大肿瘤大小相关，且仅在肿瘤复发的间质中表达。在间质或上皮以及间质胶原中高表达的versican与晚期肿瘤和骨膜蛋白的相关性较少但一致。弹性蛋白的高表达与较不严重的疾病呈负相关。高波形蛋白的相关性不一致（P值均< 0.05）。单因素分析发现，高间质骨膜蛋白是降低无进展生存期的预后因素（P = 0.007）。结论：由于在间质和上皮肿瘤间室中经常观察到上调，因此EMT-MET指示蛋白可能被整合到NSCLC的进展模型中。
Purpose: In carcinomas, invasive tumor growth is accompanied by desmoplastic stroma reaction and facilitated by epithelial-mesenchymal transition (EMT) of cancer cells. We investigated the prognostic significance of the EMT indicator proteins periostin and vimentin in comparison with versican, a putative indicator of the opposite mechanism mesenchymal-epithelial transition (MET), and to the desmoplasia proteins collagen and elastin in non-small cell lung cancer (NSCLC).Experimental Design: Tumor of 533 patients with surgically resected NSCLC was used for analysis of stromal and epithelial protein expression by immunohistochemistry (EMT-MET proteins) and Elastica van Gieson histochemical staining (Collagen and elastin). A semiquantitative sum scoring system was done on three tissue microarrays.Results: Of the 533 patients, 48% had squamous cell carcinoma, 47% adenocarcinoma, and 5% adenosquamous carcinoma. High expression of periostin in either stroma or tumor epithelia, independently scored by two pathologists, correlated with male gender, higher stage, higher pT category, and larger tumor size, and in only stroma with tumor relapse. High expression of versican in either stroma or epithelia as well as of stromal Collagen had fewer but concordant associations with advanced tumor and periostin, respectively. High expression of elastin was oppositely associated with less advanced disease. Associations of high vimentin were inconsistent (all P values < 0.05). High stromal periostin was found to be a prognostic factor for decreased progression-free survival on univariate analysis (P = 0.007).Conclusions: Because up-regulation is frequently observed in the stromal and epithelial tumor compartment, EMT-MET indicator proteins may be integrated in progression models of NSCLC.