Molecules involved in epithelial-mesenchymal transition and epithelial-stromal interaction in phyllodes tumors: implications for histologic grade and prognosis
Molecules involved in epithelial-mesenchymal transition and epithelial-stromal interaction in phyllodes tumors: implications for histologic grade and prognosis
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DOI：
10.1007/s13277-011-0296-9
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发表时间：
2012-06-01
期刊：
影响因子：
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通讯作者：
Koo, Ja Seung
中科院分区：
文献类型：
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作者：
Kwon, Ji Eun;Jung, Woo-Hee;Koo, Ja Seung
本研究的目的是研究上皮间质转化（EMT）和上皮间质相互作用（ESI）相关分子的表达，并评估其在叶状肿瘤（PT）中的作用。从207例PT标本（157例良性，34例交界性和16例恶性）中构建组织微阵列（TMA）。EMT相关标志物包括N-钙粘蛋白、Twist、TGF-β、HMGA 2、S100 A4和Ezrin以及ESI相关分子如SDF 1和CXCR 4在TMA中的存在通过化学方法进行评估。免疫组化结果进行了分析的临床病理参数。对于更高级别的PT，Twist（p < 0.001）、HMGA 2（p = 0.005）、S100 A4（p < 0.001）、CXCR 4（p < 0.001）和TGF-β（p < 0.001）的表达更高。由于PT显示较高的基质细胞构成、较高的基质有丝分裂、基质过度生长和浸润性肿瘤边缘，因此其基质组分中Twist、HMGA 2和CXCR 4的表达增加（p < 0.05）。多变量考克斯分析显示，间质组分中Twist高表达与较短的无病生存期（DFS）和总生存期（OS）相关（p < 0.001），以及较短的OS相关（p = 0.031，比值比：24.6）。总之，Twist、HMGA 2、TGF-β和S100 A4（EMT相关分子）以及CXCR 4（ESI相关分子）的表达在晚期PT的基质成分中增加。此外，Twist在间质组分中的高表达与较差的增殖相关。
The aim of this study was to investigate the expression of molecules associated with epithelial-mesenchymal transition (EMT) and epithelial-stromal interactions (ESI) and to evaluate their roles in phyllodes tumors (PTs). Tissue microarrays (TMAs) were constructed from 207 PT specimens (157 benign, 34 borderline and 16 malignant). The presence of EMT-related markers including N-cadherin, Twist, TGF-beta, HMGA2, S100A4 and Ezrin as well as ESI-related molecules such as SDF1 and CXCR4 among the TMAs was assessed immunohistochemically. Immunohistochemical results were analyzed in terms of clinicopathologic parameters. For higher grade PTs, expressions of Twist (p < 0.001), HMGA2 (p = 0.005), S100A4 (p < 0.001), CXCR4 (p < 0.001) and TGF-beta (p < 0.001) were higher. As PTs showed higher stromal cellularity, higher stromal mitosis, stromal overgrowth and infiltrative tumor margin, the expressions of Twist, HMGA2 and CXCR4 in the stromal component thereof were increased (p < 0.05). High Twist expression in the stromal component was associated with shorter disease-free survival (DFS) and overall survival (OS) (p < 0.001) as well as shorter OS in multivariate COX analysis (p = 0.031, odds ratio: 24.6). In conclusion, the expressions of Twist, HMGA2, TGF-beta and S100A4, which are EMT-associated molecules, and CXCR4, an ESI-associated molecule, were increased in the stromal component of advanced grade PTs. Further, high expression of Twist in the stromal component was correlated with poorer prognoses.