Kurokawa Hideo, Matsumoto Shinobu, Murata Tomoyuki, Yamashita Yoshihiro, Tomoyose Taiki, Zhang Min, Fukuyama Hiroshi, Takahashi Tetsu
Second Department of Oral and Maxillofacial Surgery, Kyushu Dental College, Kitakyushu 803-8580, Japan.
J Oral Pathol Med. 2003 Oct;32(9):513-21. doi: 10.1034/j.1600-0714.2003.00117.x.
Leukoplakia is an oral pre-cancerous lesion that sometimes develops into squamous cell carcinoma. Therefore, leukoplakia with epithelial dysplasia is useful for studying carcinogenesis at the cellular level. The purpose of this study was to evaluate a potential association between the loss of syndecan-1 expression and the expression of p53 protein and Ki-67 antigen, and to identify reliable markers for predicting malignant changes in oral leukoplakia with epithelial dysplasia.
Changes in the expression of syndecan-1, p53, and Ki-67 were examined immunohistochemically in 43 cases of oral leukoplakia with or without epithelial dysplasia. The subjects were categorized as: none, 13 cases; mild dysplasia, 5 cases; moderate dysplasia, 17 cases; and severe dysplasia, 8 cases. The expression of these molecules in normal oral epithelia (22 cases) was also investigated.
Strong syndecan-1 expression was observed on the surface of keratinocytes in normal epithelium. Immunopositivity was lost gradually as the extent of epithelial dysplasia increased. In normal epithelium, p53 and Ki-67 appeared mainly in the basal cell layer, while they were more widely distributed in leukoplakia. Specifically, significant changes were observed in the labeling index of p53 and Ki-67 in leukoplakia as epithelial dysplasia progressed from mild to moderate or severe.
Our results reveal that overexpression of p53 protein and Ki-67 antigen, and down-regulation of syndecan-1 expression in the lower part of the epithelium, are associated with dysplastic changes. Therefore, the down-regulation of syndecan-1 expression may be the most important reliable marker for dysplastic changes.
白斑是一种口腔癌前病变，有时会发展为鳞状细胞癌。因此，伴有上皮发育异常的白斑对于在细胞水平上研究致癌作用很有用。本研究的目的是评估syndecan-1表达缺失与p53蛋白和Ki-67抗原表达之间的潜在关联，并确定预测伴有上皮发育异常的口腔白斑恶性变化的可靠标志物。
采用免疫组织化学方法检测43例伴有或不伴有上皮发育异常的口腔白斑中syndecan-1、p53和Ki-67表达的变化。受试者分为：无发育异常，13例；轻度发育异常，5例；中度发育异常，17例；重度发育异常，8例。还研究了这些分子在正常口腔上皮（22例）中的表达。
在正常上皮的角质形成细胞表面观察到syndecan-1强表达。随着上皮发育异常程度的增加，免疫阳性逐渐消失。在正常上皮中，p53和Ki-67主要出现在基底细胞层，而在白斑中分布更广泛。具体而言，随着上皮发育异常从轻度进展为中度或重度，白斑中p53和Ki-67的标记指数出现显著变化。
我们的结果表明，上皮下部p53蛋白和Ki-67抗原的过表达以及syndecan-1表达的下调与发育异常变化有关。因此，syndecan-1表达的下调可能是发育异常变化最重要的可靠标志物。
