Loss of epithelial markers is an early event in oral dysplasia and is observed within the safety margin of dysplastic and T1 OSCC biopsies.
Loss of epithelial markers is an early event in oral dysplasia and is observed within the safety margin of dysplastic and T1 OSCC biopsies.
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DOI：
10.1371/journal.pone.0187449
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Ward CM
中科院分区：
文献类型：
--
作者：
Abdalla Z;Walsh T;Thakker N;Ward CM
口腔鳞状细胞癌（OSCC）是一种高度侵袭性的癌症，与患者的5年生存率低相关。疾病治疗进一步复杂化，因为难以预测将进展为OSCC的癌前组织和手术切除后的高复发率。在这里，我们已经评估了表达的口腔上皮标志物E-钙粘蛋白，EMP 1和5 T4和亲侵入性N-钙粘蛋白蛋白使用充分表征的抗体和定量免疫荧光显微镜在正常组织（NT），纤维上皮息肉（FEP），低度异型增生（LGD），高度异型增生（HGD），T1 OSCC和T4 OSCC活检。E-钙粘蛋白表达减少与FEP、LGD和HGD活检相关，表明E-钙粘蛋白的丢失是异常上皮内的早期事件，并且发生在没有E-到N-钙粘蛋白转换的情况下，后者仅在T4 OSCC中观察到。此外，E-钙粘蛋白和EMP 1的丢失是LGD的指标（p = 0.0006），E-钙粘蛋白、EMP 1和5 T4的丢失是HGD的指标（p = 0.0006）。E-cadherin、EMP 1和N-cadherin的表达模式可以预测LGD、HGD、T1和T4 OSCC活检组织中的异常上皮（所有疾病等级的z值= 0），并允许LGD（z = 1.47）、HGD（z = 2.138）、T1（z = 1.05）和T4 OSCC（z = 1.49）活检组织的分类。因此，这些标记物提供了一种有用的手段来预测患者活检中的异常上皮。线性回归和决定系数分析显示，NT>LGD>HGD疾病转换呈正相关，但与假定的HGD>T1 OSCC>T4 OSCC疾病转换的相关性较低。此外，在LGD、HGD和T1 OSCC患者活检的病理正常手术安全边界中E-钙粘蛋白、EMP 1、5 T4和N-钙粘蛋白的表达显示与NT显著差异，并且使用安全边界或FEP作为“正常组织”对照在所有患者队列中引入了II型错误。这项工作形成的基础上，进一步调查的作用，E-钙粘蛋白损失异常上皮细胞和自动分析用于癌症诊断的发展。
Oral squamous cell carcinoma (OSCC) is a highly aggressive cancer that is associated with poor 5-year patient survival. Disease treatment is further compounded by the difficulty in predicting pre-cancerous tissues that will progress to OSCC and the high recurrence rates following surgical resection. Here we have assessed expression of the oral epithelial markers E-cadherin, EMP1 and 5T4 and the pro-invasive N-cadherin proteins using fully characterised antibodies and quantitative immunofluorescence microscopy in normal tissue (NT), fibroepithelial polyp (FEP), low-grade dysplasia (LGD), high-grade dysplasia (HGD), T1 OSCC and T4 OSCC biopsies. Decreased E-cadherin expression was associated with FEP, LGD and HGD biopsies, demonstrating that loss of E-cadherin is an early event within abnormal epithelium and occurs in the absence of an E- to N-cadherin switch, the latter of which was only observed in T4 OSCC. Furthermore, loss of E-cadherin and EMP1 is an indicator of LGD (p = 0.0006) and loss of E-cadherin, EMP1 and 5T4 an indicator of HGD (p = 0.0006). Expression patterns of E-cadherin, EMP1 and N-cadherin could predict abnormal epithelium in LGD, HGD, T1 and T4 OSCC biopsies (z-value = 0 for all disease grades) and allowed classification of LGD (z = 1.47), HGD (z = 2.138), T1 (z = 1.05) and T4 OSCC (z = 1.49) biopsies. Therefore, these markers provide a useful means to predict abnormal epithelium in patient biopsies. Linear regression and coefficient of determination analysis revealed positive correlation with a NT>LGD>HGD disease transition but low correlation with a putative HGD>T1 OSCC>T4 OSCC disease transition. Furthermore, expression of E-cadherin, EMP1, 5T4 and N-cadherin in pathologically normal surgical safety margins of LGD, HGD and T1 OSCC patient biopsies revealed significant differences to NT and the use of safety margins or FEP as ‘normal tissue’ controls introduced Type II errors in all patient cohorts. This work forms the basis for further investigation of the role of E-cadherin loss in abnormal epithelium and in the development of automated analyses for use in cancer diagnostics.
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