Department of Pathology, Chang Gung Memorial Hospital, Linko, Chang Gung University College of Medicine, 5 Fu-Hsing Street, Kwei-Shan, Taoyuan, 333, Taiwan.
Virchows Arch. 2011 Feb;458(2):171-8. doi: 10.1007/s00428-010-0994-5. Epub 2010 Nov 3.
Cell signaling pathways play important roles in oncogenesis. Among a large number of signaling regulators in different pathways, 4E-binding protein 1 (4E-BP1) was found to be a key factor, which converges several oncogenic signals, phosphorylates the molecules, and drives the downstream proliferative signals. Recent studies showed that high expression of phosphorylated 4E-BP-1 (p-4E-BP1) is associated with poor prognosis, tumor progression, or nodal metastasis in different human cancers, but its prognostic significance in esophageal cancer remains undefined. In this study, we investigated the expression levels of p-4E-BP1 with two different phosphorylation sites Thr(37/46) and Thr(70) by immunohistochemistry and their prognostic significance in 78 cases of surgically resected esophageal squamous cell carcinoma (SCC) for the first time. We found no correlation of p-4E-BP1 expression with age, gender, preoperative concurrent chemoradiotherapy, tumor grade, pT classification, pN, pM, or pStage. Multivariate Cox regression analysis showed that high expression of p-4E-BP-1 Thr(37/46) was an independent adverse prognostic factor, with a hazard ratio of 1.73 (95% confidence interval = 1.03-2.90) and a p value of 0.038. Stratifying the patients with other prognostic factors, we found that the effect of p-4E-BP1 Thr(37/46) on survival was significant only in patients with relatively early stage disease (pT1/pT2, pN0, or pStage I/II; p = 0.0047, 0.012, and 0.011, respectively). Our data suggest that assessment of p-4E-BP1 expression could identify a subpopulation of earlier stage esophageal SCC patients with poor prognosis. These patients could be possible candidates for future studies on more aggressive treatment or target therapy.
细胞信号通路在肿瘤发生中发挥重要作用。在不同通路中的大量信号调节剂中，发现 4E 结合蛋白 1（4E-BP1）是一个关键因素，它汇聚了几种致癌信号，磷酸化分子，并驱动下游增殖信号。最近的研究表明，不同人类癌症中磷酸化 4E-BP-1（p-4E-BP1）的高表达与预后不良、肿瘤进展或淋巴结转移有关，但在食管癌中的预后意义尚不清楚。在这项研究中，我们首次通过免疫组织化学法研究了两个不同磷酸化位点 Thr（37/46）和 Thr（70）的 p-4E-BP1 的表达水平及其在 78 例手术切除的食管鳞状细胞癌（SCC）中的预后意义。我们发现 p-4E-BP1 的表达与年龄、性别、术前同期放化疗、肿瘤分级、pT 分类、pN、pM 或 p 期均无相关性。多因素 Cox 回归分析显示，高表达 p-4E-BP-1 Thr（37/46）是一个独立的预后不良因素，危险比为 1.73（95%置信区间 1.03-2.90），p 值为 0.038。对具有其他预后因素的患者进行分层分析，我们发现仅在疾病相对早期（pT1/pT2、pN0 或 p 期 I/II）的患者中，p-4E-BP1 Thr（37/46）对生存的影响才有统计学意义（p=0.0047、0.012 和 0.011）。我们的数据表明，评估 p-4E-BP1 的表达可以识别出预后不良的早期阶段食管 SCC 患者亚群。这些患者可能是未来更积极治疗或靶向治疗研究的潜在候选者。
