Remodeling of the Epithelial-Connective Tissue Interface in Oral Epithelial Dysplasia as Visualized by Noninvasive 3D Imaging.
Remodeling of the Epithelial-Connective Tissue Interface in Oral Epithelial Dysplasia as Visualized by Noninvasive 3D Imaging.
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DOI：
10.1158/0008-5472.can-16-0252
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发表时间：
2016-08-15
期刊：
影响因子：
11.2
通讯作者：
Vargas G
中科院分区：
文献类型：
--
作者：
Pal R;Shilagard T;Yang J;Villarreal P;Brown T;Qiu S;McCammon S;Resto V;Vargas G
口腔上皮异型增生的早期肿瘤特征首先在位于上皮-结缔组织界面（ECTI）的基底上皮处明显，将基底上皮与下面的固有层分离。由于局部上皮扩张和固有层的蛋白水解重塑，ECTI在早期瘤形成中发生显著变形，但很少有研究检查这些变化。在本研究中，我们使用体内体积多光子自体荧光显微镜和二次谐波发生显微镜定量分析了异型增生中ECTI地形图的变化。无标记方法允许直接非侵入性可视化的ECTI表面，而不扰动上皮。描述了一种基于图像的参数“ECTI轮廓”，其指示ECTI表面的变形。发育异常的ECTI轮廓高于对照或炎症样本，表明表面从平坦过渡到变形。测量基底上皮细胞核面积、核密度、核面积变异系数和ECTI邻近区域胶原密度等细胞参数。ECTI轮廓区分异型增生与对照/良性粘膜的敏感性和特异性高于基底核密度或基底核面积，与核面积和胶原密度的变异系数相当。所提出的方法提供了一个独特的机会，研究ECTI在完整的粘膜细胞和细胞外基质功能的同时评估，扩大机会，研究早期肿瘤事件附近的这个关键接口，并可能导致新的方法在体内检测肿瘤的发展。
Early neoplastic features in oral epithelial dysplasia are first evident at the basal epithelium positioned at the epithelial-connective tissue interface (ECTI), separating the basal epithelium from the underlying lamina propria. The ECTI undergoes significant deformation in early neoplasia due to focal epithelial expansion and proteolytic remodeling of the lamina propria but few studies have examined these changes. In the present study, we quantitated alterations in ECTI topography in dysplasia using in vivo volumetric multiphoton autofluorescence microscopy and second harmonic generation microscopy. The label-free method allows direct noninvasive visualization of the ECTI surface without perturbing the epithelium. An image-based parameter, ‘ECTI contour’, is described that indicates deformation of the ECTI surface. ECTI contour was higher in dysplasia than control or inflammed specimens, indicating transition from flat to a deformed surface. Cellular parameters of nuclear area, nuclear density, coefficient of variation in nuclear area in the basal epithelium and collagen density in areas adjacent to ECTI were measured. ECTI contour differentiated dysplasia from control/benign mucosa with higher sensitivity and specificity than basal nuclear density or basal nuclear area, comparable to coefficient of variation in nuclear area and collagen density. The presented method offers a unique opportunity to study ECTI in intact mucosa with simultaneous assessment of cellular and extracellular matrix features, expanding opportunities for studies of early neoplastic events near this critical interface and potentially leading to development of new approaches for detecting neoplasia in vivo.