Evaluation of CD44 and TGF-B Expression in Oral Carcinogenesis

STATEMENT OF THE PROBLEM: Oral squamous cell carcinoma (OSCC) is the most common malignancy of the oral cavity. Early diagnosis of OSCC by using biomarkers provides preventive treatment approach to suppress the disease in early stages. CD44 as a cancer stem cell (CSC) marker may be cleaved by MT1-MMP and plays an important role in migration of cancer cells. TGF-B promotes formation of invasive cancer cells phenotype through epithelial mesenchymal transition (EMT) and induces MT1-MMP formation. PURPOSE: The aim of this study was to evaluate the expression of TGF-B and CD44 in leukoplakia (premalignant lesion), squamous cell carcinoma (SCC), and normal oral mucosa to determine the role of these markers in the carcinogenesis process of the oral mucosa. MATERIALS AND METHOD: In this retrospective study, the expression of TGF-B and CD44 were evaluated in 55 paraffin-embedded specimens (10normal mucosa, 15 non-dysplastic leukoplakia, 15 dysplastic leukoplakia, and 15 OSCC) by immunohistochemistry. Statistical analyses were performed using Kruskal-Wallis, Mann-Whitney, and Spearman’s rank correlation tests. RESULTS: Evaluation of CD44 and TGF-B expression in the four studied groups showed statistical significant difference for each marker (p< 0.001). Pairwise comparison of CD44 and TGF-B expression in all groups except normal mucosa and non-dysplastic leukoplakia demonstrated statistical significant difference. In addition, there was positive significant correlation between two markers (r= 0.914, p< 0.001). Diagnostic test’s accuracy for identification of OSCC and dysplastic leukoplakia from non-dysplastic leukoplakia and normal tissues and recognition of OSCC from dysplastic leukoplakia showed optimum sensitivity and specificity. CONCLUSION: Increased expression of CD44 as a cancer stem cell marker and TGF-B as an EMT marker from normal mucosa to non-dysplastic leukoplakia, dysplastic leukoplakia, and OSCC and also the significant correlation between these two markers indicated their role in carcinogenesis of oral mucosa.