Bhardwaj Mansi, Sen Seema, Sharma Anjana, Kashyap Seema, Chosdol Kunzang, Pushker Neelam, Bajaj Mandeep Singh, Bakhshi Sameer
Department of Ocular Pathology, Dr Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi 110029, India.
Department of Ocular Microbiology, Dr Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi 110029, India.
Hum Pathol. 2015 Oct;46(10):1437-42. doi: 10.1016/j.humpath.2015.05.026. Epub 2015 Jun 10.
Epithelial-mesenchymal transition (EMT) plays a pivotal role in tumor invasion and metastasis in various malignancies. ZEB2/SIP1 is an important EMT regulator and down-regulates E-cadherin expression. The present study was planned to explore status of EMT-associated markers ZEB2/SIP1 and E-cadherin in eyelid sebaceous gland carcinoma (SGC) and to correlate with clinicopathological high-risk features. Expressions of ZEB2 and E-cadherin were evaluated by immunohistochemistry in 65 cases of histopathologically proven eyelid SGC. The results were correlated with clinicopathological high-risk features and survival of the patients to determine the prognostic significance of ZEB2, E-cadherin, and various high-risk features. Cytoplasmic overexpression of ZEB2 and membranous loss of E-cadherin were seen in 68% and 66% of cases of eyelid SGC, respectively. ZEB2 overexpression was significantly associated with E-cadherin loss (P = .002). Overexpression of ZEB2 also showed significant association with lymph node metastasis (P = .046), orbital invasion (P = .049), large tumor size (P = .018), and advanced tumor stages (P = .036). Survival analysis revealed that patients with ZEB2 overexpression had poor survival. ZEB2 overexpression and orbital invasion were found to be independent prognostic indicators (univariate analysis). However, multivariate analysis showed that ZEB2 (hazard ratio, 0.094; 95% confidence interval, 00.012-0.709; P = .022) was the best poor prognostic indicator of eyelid SGC. Our study demonstrates the role of both ZEB2 and E-cadherin in the promotion of EMT in eyelid SGC. The outcome of this study also points toward ZEB2 as an independent prognostic marker as well as a potential therapeutic target in eyelid SGC.
上皮-间质转化（EMT）在多种恶性肿瘤的肿瘤侵袭和转移中起关键作用。ZEB2/SIP1是一种重要的EMT调节因子，可下调E-钙黏蛋白的表达。本研究旨在探讨EMT相关标志物ZEB2/SIP1和E-钙黏蛋白在眼睑皮脂腺癌（SGC）中的状态，并与临床病理高危特征相关联。通过免疫组织化学评估65例经组织病理学证实的眼睑SGC中ZEB2和E-钙黏蛋白的表达。将结果与临床病理高危特征和患者生存率相关联，以确定ZEB2、E-钙黏蛋白和各种高危特征的预后意义。在68%的眼睑SGC病例中可见ZEB2的细胞质过表达，在66%的病例中可见E-钙黏蛋白的膜性缺失。ZEB2过表达与E-钙黏蛋白缺失显著相关（P = 0.002）。ZEB2的过表达还与淋巴结转移（P = 0.046）、眼眶侵犯（P = 0.049）、肿瘤体积大（P = 0.018）和肿瘤晚期（P = 0.036）显著相关。生存分析显示，ZEB2过表达的患者生存率较差。发现ZEB2过表达和眼眶侵犯是独立的预后指标（单因素分析）。然而，多因素分析显示ZEB2（风险比，0.094；95%置信区间，0.012 - 0.709；P = 0.022）是眼睑SGC最佳的不良预后指标。我们的研究证明了ZEB2和E-钙黏蛋白在促进眼睑SGC的EMT中的作用。本研究结果还表明ZEB2是眼睑SGC的独立预后标志物以及潜在的治疗靶点。
