A Histopathological and Immunohistochemical Study of Cell-Cell Interactions : With Special Reference to Advance of Dysplastic Grading

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A histopathological and immunohistochemical study was conducted to elucidate the changes in cell-cell interactions and important related factors in oral precursor lesions and oral squamous cell carcinoma (OSCC). Gingivae from 36 cases (5 healthy epithelium, 7 hyperkeratosis, 7 mild dysplasia, 7 moderate dysplasia, 5 severe dysplasia, and 5 OSCC) were examined. From immunohistochemical analysis, the positive distribution of E-cadherin was observed as pericellular meshes that strongly appeared in the upper spinosum layer in moderate dysplasia, decreased in severe dysplasia, and disappeared in OSCC. Integrin α6 gradually expanded to all spinosum layers with the advance of dysplastic grading. Weakly irregular distribution was observed in all tumor cells of OSCC. Epidermal growth factor receptor (EGFR) was shown in the spinosum layer of mild dysplasia, expanded with the advance of dysplastic grading, and was seen in all tumor cells in OSCC. Anti-lysyl oxidase (LOX) gradually increased with the advance of dysplastic grading. Perlecan showed similar results to LOX except that was decreased in OSCC. Briefly, the loss of E-cadherin in the lower half of the spinosum layer, integrin α6 in the spinosum layer with lost polarity, and the appearance of EGFR in the basal layer were observed in moderate dysplasia. Furthermore, LOX and perlecan distributions were frequently found in high-grade dysplastic lesions. The present study of oral precursor lesions found that instability or decreased cell adhesion related to the environment was observed in moderate dysplasia and higher grades of dysplasia. Consequently, it was supposed that moderate dysplasia was the stage at which lesions became tumorous.