Immunoexpression of C4 Binding Protein in Oral Leukoplakia and Oral Squamous Cell Carcinoma.

BACKGROUND: The immune evasion of dysplastic cells plays an important role in suppressing the immune response and progression of malignancy. The role of the complement inhibitors in the development of oral epithelial dysplastic lesions and squamous cell carcinoma (SCC) is still unclear. OBJECTIVE: This study aimed to assess the expression of C4 binding protein (C4BP) as a complement inhibitor in oral squamous cell carcinoma and leukoplakia. METHODS: In this study, 94 samples were classified into four groups: leukoplakia with mild to moderate dysplasia, leukoplakia with severe dysplasia or carcinoma in situ, early invasive SCC, and invasive SCC. The expression of C4BP marker was evaluated by immunohistochemistry (IHC) and real-time PCR. The results were analyzed by the Kruskal-Wallis, Bonferroni adjusted Dunn's multiple comparison, and one-way ANOVA tests. RESULTS: The results of IHC revealed the expression patterns of C4BP in oral dysplasia and SCC, and indicated that the C4BP expression was not significantly different between different histopathological grades in epithelial cells and vessels (P=0.157 and P=0.123, respectively) but, it was significantly different in fibroblasts and lymphocytes (P=0.017 and P=0.043, respectively). The real-time PCR showed a significant correlation between the dysplasia grade and expression of C4BP (P<0.05). CONCLUSION: According to the results, C4BP is expressed in the cancerous tissue by the tumor cells and their surrounding stroma. In addition, upregulation of the C4BP gene as an inhibitor of the complement system is a possible strategy adopted by the tumor cells to evade the immune system.

Correlation of Vascularization and Inflammation with Severity of Oral Leukoplakia.

BACKGROUND & OBJECTIVE: Changes in submucosal vascularization and inflammation, determined by immunohistochemistry staining, were shown to be correlated with the development of dysplasia and invasiveness of epithelial cells in premalignant and malignant lesions. This study evaluated changes in sections routinely stained with Hematoxylin and Eosin (H&E) in order to investigate vascular density and intensity of inflammatory cells infiltration during the progression of oral leukoplakia with mild dysplasia to Squamous Cell Carcinoma (SCC).The aim of the research was to determine whether changes in sub-mucosal vascularity and inflammatory infiltration of leukoplakia in routine H&E-stained sections could contribute to the assessment of severity of the lesion. METHODS: In this cross-sectional, comparative and descriptive study, vascular density and inflammation intensity of 125 available samples of H&E-stained sections, consisting of 35 cases of mild and moderate dysplasia, 38 severe dysplasia and carcinoma in situ, and 52 SCC, were investigated. To analyze the data, chi-square test, Mann-Whitney test, Kruskal-Wallis test, Tukey's post hoc test, and cumulative ordinal logistic regression were conducted. RESULTS: There was a significantly higher vascular density in cases with severe dysplasia, in situ carcinoma, and SCC compared to those with mild to moderate dysplasia (P<0.0001). However, the difference in vascularity was not statically significant between severe dysplasia, carcinoma in situ, and SCC (P=0.78). Intensity of inflammatory cells infiltration in the underlying connective tissue was significantly different among the three groups (P<0.0001), and the highest intensity of inflammatory cells infiltration was seen in the SCC group. CONCLUSIONS: Increased submucosal vascularization and inflammatory cells infiltration can contribute further to predicting more aggressive epithelial dysplasia.