Immunohistochemical study of syndecan-1 down-regulation and the expression of p53 protein or Ki-67 antigen in oral leukoplakia with or without epithelial dysplasia.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Kurokawa
Hideo
H
Second Department of Oral and Maxillofacial Surgery, Kyushu Dental College, Kitakyushu 803-8580, Japan. kuro@kyu-dent.ac.jp
Matsumoto
Shinobu
S
Murata
Tomoyuki
T
Yamashita
Yoshihiro
Y
Tomoyose
Taiki
T
Zhang
Min
M
Fukuyama
Hiroshi
H
Takahashi
Tetsu
T
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D002471:Cell Transformation, Neoplastic / Q000473:pathology; D018450:Disease Progression; D015536:Down-Regulation; D004848:Epithelium / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D015603:Keratinocytes / Q000473:pathology; D019394:Ki-67 Antigen / Q000032:analysis*; D007972:Leukoplakia, Oral / Q000473:pathology*; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis*; D008875:Middle Aged; D009061:Mouth Mucosa / Q000473:pathology; D009062:Mouth Neoplasms / Q000473:pathology*; D011509:Proteoglycans / Q000032:analysis*; D018709:Statistics, Nonparametric; D053668:Syndecan-1; D053667:Syndecans; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*
D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D008562:Membrane Glycoproteins; D011509:Proteoglycans; C508241:SDC1 protein, human; D053668:Syndecan-1; D053667:Syndecans; D016159:Tumor Suppressor Protein p53