The expression of c-Met pathway components in unclassified pleomorphic sarcoma/malignant fibrous histiocytoma (UPS/MFH): a tissue microarray study.
The expression of c-Met pathway components in unclassified pleomorphic sarcoma/malignant fibrous histiocytoma (UPS/MFH): a tissue microarray study.
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c-Met 通路成分在未分类的多形性肉瘤/恶性纤维组织细胞瘤 (UPS/MFH) 中的表达：组织微阵列研究。
DOI：
10.1111/j.1365-2559.2011.03946.x
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发表时间：
2011
期刊：
影响因子：
6.4
通讯作者：
Lev,Dina
中科院分区：
文献类型：
--
作者：
Lahat,Guy;Zhang,Pingyu;Zhu,Quan-Sheng;Torres,Keila;Ghadimi,Markus;Smith,KerringtonD;Wang,Wei-Lien;Lazar,AlexanderJ;Lev,Dina
Lahat G，Zhang P，Zhu Q-S，托雷斯K，Ghadimi M，Smith K D，Wang W-L，Lazar A J & Lev D（2011）Histology 59，556- 561未分类的多形性肉瘤/恶性纤维组织细胞瘤（UPS/MFH）中c-Met途径组分的表达：组织微阵列研究目的：基于分子标志物的表达模式将未分化的多形性肉瘤/恶性纤维组织细胞瘤（UPS/MFH）亚分类为不同的生物学群组可以鉴定具有特别不利的临床结果的患者亚群。
鉴定适于药物靶向的分子调节剂可以促进UPS/MFH定制疗法的合理开发。方法和结果：在158个UPS/MFH样本的临床注释组织微阵列上进行肝细胞生长因子（HGF）、c-Met、磷酸-c-Met（pc-Met）、磷酸促分裂原活化蛋白激酶激酶（MAPKK）（也称为促分裂原活化蛋白激酶（MAPK）/细胞外信号调节激酶（ERK）激酶（p-MEK））和磷酸蛋白激酶B（p-AKT）的免疫组织化学分析。进行单变量和多变量分析以评估分子变量与UPS/MFH疾病特异性生存的相关性。所有评价的标志物在UPS/MFH中表达至不同水平。最重要的是，在单变量统计分析中，HGF、pc-Met、p-MEK和p-AKT的强表达与患者的不良结局显著相关。p-MEK和p-AKT的表达在多变量分析中仍然是统计学显著的独立预测因子。结论：c-Met通路组分，特别是p-MEK和p-AKT是UPS/MFH的潜在预后生物标志物;应评估其是否纳入未来的分子分期系统。此外，针对一部分UPS/MFH患者，应考虑使用靶向HGF、c-Met、MEK/细胞外调节激酶（ERK）和/或AKT的新方法。
Lahat G, Zhang P, Zhu Q‐S, Torres K, Ghadimi M, Smith K D, Wang W‐L, Lazar A J & Lev D
(2011)Histopathology59, 556–561The expression of c‐Met pathway components in unclassified pleomorphic sarcoma/malignant fibrous histiocytoma (UPS/MFH): a tissue microarray studyAims:Subclassification of undifferentiated pleomorphic sarcoma/malignant fibrous histiocytoma (UPS/MFH) into distinct biological cohorts based on the expression patterns of molecular markers can identify patient subsets with especially unfavourable clinical outcomes. Identification of molecular prognosticators amenable for drug targeting can facilitate rational development of UPS/MFH tailored therapies. The aim was to evaluate expression of c‐Met pathway components in a large cohort of UPS/MFH samples.Methods and results:An immunohistochemical analysis for hepatocyte growth factor (HGF), c‐Met, phospho‐c‐Met (pc‐Met), phospho‐mitogen‐activated protein kinase kinase (MAPKK) also known as mitogen‐activated protein kinase (MAPK)/extracellular signal‐regulated kinase (ERK) kinase (p‐MEK) and phospho‐protein kinase B (p‐AKT) was performed on a clinically annotated tissue microarray of 158 UPS/MFH samples. Univariable and multivariable analyses were conducted to evaluate the correlation of molecular variables with UPS/MFH disease specific survival. All evaluated markers were expressed in UPS/MFH to varying levels. Most importantly, strong HGF, pc‐Met, p‐MEK and p‐AKT expression correlated significantly with dismal patient outcome on univariable statistical analysis. Expression of p‐MEK and p‐AKT remained statistically significant independent prognosticators on multivariable analysis.Conclusions:c‐Met pathway components and especially p‐MEK and p‐AKT are potential prognostic biomarkers for UPS/MFH; their inclusion in future molecular‐based staging systems should be evaluated. Furthermore, novel approaches targeting HGF, c‐Met, MEK/extracellular‐regulated kinase (ERK) and/or AKT should be considered for a subset of UPS/MFH patients.