Desmosomal component expression in normal, dysplastic, and oral squamous cell carcinoma

Abstract

Squamous cell carcinoma (oral SCC) is the most common oral cancer in the U.S., affecting nearly 30,000 Americans each year. Despite recent advances in detection and treatment, there has been little improvement in the five-year survival rate for this devastating disease. Oral cancer may be preceded by premalignant disease that appears histologically as dysplasia. Identification of molecular markers for cellular change would assist in determining the risk of dysplasia progressing to oral squamous cell carcinoma. The goal of this study was to determine if any correlation exists between histological diagnosed dysplasia and OSCC lesions and altered expression of desmosomal cell-cell adhesion molecules in the oral epithelium. Our data showed that oral SCC tissue samples showed decreased immunoreactivity of both desmoplakin and plakophilin-1 proteins compared to normal oral epithelium. Furthermore, significant decrease in desmoplakin immunoreactivity was observed in dysplastic tissue compared to normal oral epithelium. In contrast, the level of desmoglein-1 staining was unchanged between samples however desmoglein-1 was found localized to cell borders in oral SCC samples. These data suggest that changes in expression of desmoplakin and plakophilin-1 may prove to be a useful marker for changes in tissue morphology and provide a tool for identifying pre-neoplastic lesions of the oral cavity.

Figure 1

Morphologic evaluation of normal oral mucosa (a), dysplastic oral mucosa (b), and oral squamous cell carcinoma (c). Representative sections were stained with Hematoxylin and eosin to verify the initial diagnosis of the tissue blocks used in the present study.

Figure 2

Representative antidesmoplakin staining of oral tissues. Antidesmoplakin monoclonal antibody (10F6) was used to stain normal oral mucosa (a), dysplastic oral mucosa (b), and oral squamous cell carcinoma (c). Normal oral mucosa processed in the absence of primary antibody serves as a negative control (d). The scale bar in panel A corresponds to 20 μm.

Figure 3

Representative antiplakophilin-1 staining of oral tissues. Antiplakophilin-1 monoclonal antibody (14B11) was used to stain normal oral mucosa (a), dysplastic oral mucosa (b), and oral squamous cell carcinoma (c). Normal oral mucosa processed in the absence of primary antibody serves as a negative control (d). The scale bar in panel A corresponds to 20 μm.

Figure 4

Representative anti-desmoglein-1 staining of oral tissues. Anti-desmoglein-1 monoclonal antibody (27B2) was used to stain normal oral mucosa (a), dysplastic oral mucosa (b), and oral squamous cell carcinoma (c). Normal oral mucosa processed in the absence of primary antibody serves as a negative control (d). The scale bar in panel A corresponds to 10 μm.

Figure 5

Semiquantitative scoring of desmosomal component expression. Relative intensity of desmoplakin, plakophilin-1, and desmoglein-1 was scored by three observers and the average score is presented (+ or − the standard error) for normal oral mucosa (N), dysplastic epithelium (D), and oral squamous cell carcinoma (S) (* :  z value >2.394 indicate significant difference).