Epithelial-mesenchymal transition (EMT) and activated extracellular signal-regulated kinase (p-Erk) in surgically resected pancreatic cancer
Epithelial-mesenchymal transition (EMT) and activated extracellular signal-regulated kinase (p-Erk) in surgically resected pancreatic cancer
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DOI：
10.1245/s10434-007-9540-3
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发表时间：
2007-12-01
影响因子：
3.7
通讯作者：
Khoury, T.
中科院分区：
文献类型：
--
作者：
Javle, M. M.;Gibbs, J. F.;Khoury, T.
背景：EMT或向间充质表型转化在肿瘤侵袭转移中起重要作用。体外实验数据表明，间充质转化可能与PI3激酶和Ras/Erk信号通路的激活有关。我们研究了EMT标志物(低E-钙粘蛋白、高纤维连接蛋白和波形蛋白)在胰腺癌组织中的表达及其与p-ERK的关系。方法：收集34例胰腺癌患者的临床资料和手术标本。用抗波形蛋白、纤维连接蛋白、E-钙粘蛋白和p-Erk的单抗对福尔马林固定的石蜡包埋组织进行免疫组织化学染色。其结果与临床病理参数和生存期相关。生存分析(对数等级检验、COX比例风险模型)、分类资料分析(皮尔逊卡方检验、Fisher精确检验)和Kendall‘s tau检验。结果：病例组男性13例，女性21例，年龄中位数66岁(38~84岁)，美国癌症联合委员会(AJCC)第1期2例，第2期27例，第3期5例；组织学分级1级4例，2级13例，3级16例，4级1例。中位生存期为15个月(95%可信区间：11~24个月)。纤维连接蛋白的过度表达与波形蛋白(p=0.0048)和激活的ERK(p=0.0264)相关。纤维粘连蛋白的表达与肿瘤分级呈交界性相关(p=0.06)。波形蛋白与上皮钙粘附素呈负相关(p=0.0024)。纤维连接蛋白或波形蛋白的升高和E-钙粘附素的降低与胰腺癌的生存不良相关。结论：胰腺癌手术切除后的EMT与生存不良有关。激活的ERK和纤维连接蛋白之间的相关性被确定，这可能为这一亚群的靶向治疗开辟道路。
Background: EMT or transformation to the mesenchymal phenotype plays an important role in tumor invasion and metastasis. In vitro data suggest that mesenchymal transformation may correlate with the activation of PI3 kinase and Ras/Erk pathways. We investigated the expression of EMT markers (low E-cadherin, high fibronectin, and vimentin) and their association with p-Erk in resected pancreatic cancer.Methods: Clinical data/surgical specimens from 34 consecutive pancreatic cancer patients (pts) who underwent pancreatectomy were included. Immunohistochemical staining was performed on formalin-fixed paraffin-embedded tissues using monoclonal antibodies against vimentin, fibronectin, E-cadherin, and p-Erk. The results were correlated with clinicopathological parameters and survival. Survival analysis (log-rank test, Cox proportional hazard model), categorical data analysis (Pearson's chi-square, Fisher's exact test) and Kendall's tau were performed at a significance level of 0.05.Results: The patient population was formed from 13 males and 21 females, with a median age of 66 years (range 38-84 years); American Joint Committee on Cancer (AJCC) stage 1 (n = 2), 2 (n = 27), 3 (n = 5); histological grade 1 (n = 4), 2 (n = 13), 3 (n = 16), 4 (n = 1). Median survival was 15 months (95% CI: 11-24 months). Fibronectin overexpression correlated with the presence of vimentin (p = 0.0048) and activated Erk (p = 0.0264). There was a borderline association of fibronectin with worsening grade (p = 0.06). A negative association between vimentin and E-cadherin was noted (p = 0.0024). Increased fibronectin or vimentin and decreased E-cadherin correlated with poor survival.Conclusion: EMT is associated with poor survival in surgically resected pancreatic adenocarcinoma. A correlation between activated Erk and fibronectin was identified that may open avenues for targeted therapy for this subgroup.