The notch pathway is activated in neoplastic progression in esophageal squamous cell carcinoma
The notch pathway is activated in neoplastic progression in esophageal squamous cell carcinoma
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DOI：
10.1016/j.humpath.2017.11.004
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发表时间：
2018-02-01
期刊：
影响因子：
3.3
通讯作者：
Furth, Emma E.
中科院分区：
文献类型：
--
作者：
Lubin, Daniel J.;Mick, Rosemarie;Furth, Emma E.
Notch 信号通路是人类正常发育和体内平衡不可或缺的一部分，并且对细胞分化具有确定性功能。最近的研究表明，异常的 Notch 信号传导可能通过增加干细胞存活、化疗耐药性和促进上皮间质转化而促进肿瘤进展。我们研究的目的是利用定量技术确定食管鳞状细胞癌 (SCC) 中激活的 Notch 1 的表达，并确定 Notch 1 表达与各种临床病理参数之间的关系。对2007年至2015年在我科诊断的连续60例食管鳞状细胞癌、42例良性食管鳞状上皮和13例嗜酸粒细胞性食管炎进行了Notch细胞内结构域（NICD）的免疫组织化学染色，并使用Vectra成像系统对准确的核染色和核特征进行了分级。收集每个 SCC 病例的临床病理数据（性别、诊断时年龄、吸烟状况、肿瘤分级、肿瘤分期、肿瘤位置和生存率），并将这些数据与 NICD 染色相关。与良性和反应性食管上皮病例相比，食管鳞状细胞癌病例表现出明显更高的 NICD 染色（分别为 P = 0.003 和 0.005）。在食管 SCC 病例中，核 NICD 染色与肿瘤分级和分期显着相关。经过分类和回归树分析，发现 NICD 表达增加的食管 SCC 患者比表达水平较低的患者更容易死于疾病。综上所述，研究结果表明，Notch 1 的增加可能有助于食管鳞状细胞癌的发展和侵袭性。 (C) 2017 Elsevier Inc. 保留所有权利。
The Notch signaling pathway is integral to normal human development and homeostasis and has a deterministic function on cell differentiation. Recent studies suggest aberrant Notch signaling may contribute to neoplastic progression by an increase in stem cell survival, chemoresistance, and the promotion of epithelial-to-mesenchymal transition. The goals of our study were to determine, utilizing quantitative technologies, the expression of activated Notch 1 in esophageal squamous cell carcinoma (SCC) and to determine the relationship between Notch 1 expression and various clinicopathologic parameters. Immunohistochemical staining for Notch intracellular domain (NICD) was performed on 60 consecutive cases of esophageal squamous cell carcinoma, 42 cases of benign esophageal squamous epithelium, and 13 cases of eosinophilic esophagitis diagnosed in our department from 2007 through 2015, and exact nuclear staining and nuclear characteristics were graded using the Vectra imaging system. Clinicopathologic data (gender, age at diagnosis, smoking status, tumor grade, tumor stage, tumor location, and survival) were collected for each SCC case and these were correlated with NICD staining. Cases of esophageal SCC demonstrated significantly higher NICD staining compared to cases of benign and reactive esophageal epithelium (P = .003 and .005, respectively). Among cases of esophageal SCC, nuclear NICD staining was significantly correlated with both tumor grade and stage. Following classification and regression tree analysis, esophageal SCC patients with increased NICD expression were found to be more likely to die from their disease than those with lower levels of expression. Taken together, the findings suggest that increased Notch 1 may contribute to the development and aggressiveness of esophageal SCC. (C) 2017 Elsevier Inc. All rights reserved.