Department of Pathology, Hospital of the University of Pennsylvania, Philadelphia, PA, 19104.
Department of Biostatistics and Epidemiology, Perelman School of Medicine, The University of Pennsylvania, Philadelphia, PA, 19104.
Hum Pathol. 2018 Feb;72:66-70. doi: 10.1016/j.humpath.2017.11.004. Epub 2017 Nov 12.
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.
Notch 信号通路对于正常的人类发育和内稳态至关重要，对细胞分化具有决定性作用。最近的研究表明，异常的 Notch 信号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。我们的研究目的是利用定量技术确定食管鳞状细胞癌（SCC）中激活的 Notch1 的表达，并确定 Notch1 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 60 例连续食管鳞状细胞癌、42 例良性食管鳞状上皮和 13 例嗜酸性食管炎病例进行 Notch 细胞内结构域（NICD）的免疫组织化学染色，使用 Vectra 成像系统对核染色和核特征进行精确分级。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、肿瘤位置和生存情况），并将其与 NICD 染色相关联。食管 SCC 病例的 NICD 染色明显高于良性和反应性食管上皮病例（分别为 P=.003 和 P=.005）。在食管 SCC 病例中，核 NICD 染色与肿瘤分级和分期均显著相关。通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有可能死于该病。总之，这些发现表明 Notch1 的增加可能有助于食管 SCC 的发展和侵袭性。
