Department of Surgery, Cancer Comprehensive Center Vienna, University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.
Clin Exp Metastasis. 2012 Aug;29(6):615-24. doi: 10.1007/s10585-012-9475-3. Epub 2012 Apr 8.
The signal-transcriptional factor signal transducer and activator of transcription (STAT3) is overexpressed in various tumor entities and promotes tumor progression and metastasis. The tyrosine-kinase receptor Her-2 was shown to activate STAT3-expression and is overexpressed in a subtype of esophageal cancer (EC). STAT3 also regulates carbonic anhydrase IX (CAIX) expression in vivo, promoting IL-6-dependent tumor invasion.Tumor-tissue from 324 patients with EC and 45 patients with precursor lesions were analyzed for the expressions of tyrosine-705 phosphorylated STAT3 (pSTAT3). Data on Her-2-status and CAIX expression were available from previous studies. pSTAT3 was overexpressed in 40 % of adenocarcinomas (AC) and 50 % of squamous cell carcinomas of the esophagus and was associated with worse overall (OS) (p = 0.001) and disease free survival (DFS) (p = 0.001). In Barrett's mucosa without/low-grade dysplasia, pSTAT3 was expressed in 14 % compared to 27 % in patients with high-grade dysplasia (p = 0.018). A significant association between Her-2 and pSTAT3 was found in ACs (p = 0.013), showing that patients with tumors expressing both proteins have significantly worse OS (p = 0.0039) and DFS (p = 0.029). One hundred-fifty (46.3 %) cancer cases were considered as positive for CAIX expression, and a strong correlation between pSTAT3 and CAIX expression was seen (p < 0.001). pSTAT3 plays an important role in the development of AC. Expression of pSTAT3 correlates with Her-2 status and CAIX expression and is associated with tumor progression and worse outcome, offering expectantly therapeutical implications.
信号转导和转录激活因子 3（STAT3）在各种肿瘤实体中过度表达，促进肿瘤的进展和转移。酪氨酸激酶受体 Her-2 被证明可以激活 STAT3 的表达，并在食管癌（EC）的一个亚型中过表达。STAT3 还调节体内碳酸酐酶 IX（CAIX）的表达，促进 IL-6 依赖性肿瘤侵袭。分析了 324 例 EC 患者和 45 例癌前病变患者的肿瘤组织中酪氨酸 705 磷酸化 STAT3（pSTAT3）的表达。先前的研究中提供了有关 Her-2 状态和 CAIX 表达的数据。pSTAT3 在腺癌（AC）的 40%和食管鳞癌的 50%中过表达，与总生存期（OS）（p = 0.001）和无病生存期（DFS）（p = 0.001）较差相关。在无/低级别异型增生的 Barrett 黏膜中，pSTAT3 的表达率为 14%，而高级别异型增生患者的表达率为 27%（p = 0.018）。在 AC 中发现 Her-2 和 pSTAT3 之间存在显著相关性（p = 0.013），表明同时表达这两种蛋白的患者的 OS（p = 0.0039）和 DFS（p = 0.029）显著更差。有 150 例（46.3%）癌症病例被认为 CAIX 表达阳性，并且 pSTAT3 与 CAIX 表达之间存在很强的相关性（p < 0.001）。pSTAT3 在 AC 的发展中起重要作用。pSTAT3 的表达与 Her-2 状态和 CAIX 表达相关，与肿瘤进展和不良预后相关，有望提供治疗意义。
