Expression of cluster differentiation-44 stem cell marker in grades of oral epithelial dysplasia: A preliminary study

Abstract

Introduction: Oral cancer is one among the alarming diseases related to oral cavity. Its prevalence and incidence have increased in many folds, in the past decade. This has led the investigators to find the preliminary stages and related early evaluating methods to restrain it. Few clinical lesions such as leukoplakia, erythroplakia, oral submucous fibrosis and lichen planus reflected malignant changes. These premalignant disorders provided scope to assess the underlying cellular and molecular events, which shall be helpful in early detection, aggressiveness and prognosis of the patient. Materials and Methods: Forty formalin fixed, paraffin embedded blocks were utilized and evenly subdivided into Group I – control tissue, Group II – mild epithelial dysplasia, Group III – moderate epithelial dysplasia and Group IV – severe epithelial dysplasia. The study group was categorized based on the WHO classification of dysplasia 2005. Routine staining was performed to reconfirm the diagnosis of all the samples. Simultaneously, immunohistochemical staining was done with cluster differentiation-44 (CD44) antibody. Positive cells were counted on 10 representative fields with a minimum of 100 cells per field using ×20. Statistical Analysis: Comparison of four groups with respective to number of positive cells was done using Kruskal–Wallis ANOVA test. Pair-wise comparison of three grades of oral epithelial dysplasia and the controls was done using Mann–Whitney U test. Results: The mean of Group I is 745.50, Group II is 665.20, Group III is 530.10 and Group IV is 322.90. A statistically significant P = 0.00001 was ascertained on comparison of the mean between the groups. Conclusion: CD44, a cell membrane marker could help in cell adhesion and cell-cell interactions. Loss of CD44 expression enhances the binding of the growth factors with their principle receptors that enhances the cellular proliferation. It can be used as a prognostic marker for identifying the rate of malignant transformation in these disorders.

Correlation of Soluble CD44 Expression in Saliva and CD44 Protein in Oral Leukoplakia Tissues

“…As we know, the CD44 protein belongs to the stem cell group, and describes the localization in epithelium, the mediation of adhesive properties, and signals for the orientation of epithelial cells to migrate upward. This coincides with the data of other authors [24,29,[83][84][85].…”

“…Most researchers have described the intra-cytoplasmatic pattern of the CD44 expression in real, invasive oral cancers [86], but few have diagnosed its expression in the cytoplasm of the oral epithelium in leukoplakia and explained it considering the interaction of the CD44 antigen with the cytoskeleton [29,[87][88][89]. However, other studies are contradictory, for example, the study of Naga et al [24]. Severe epithelial dysplasia cases showed down-regulated CD44 expression.…”

“…The cleaved extracellular region is either secreted into the fluid phase or sequestered to the extracellular matrix [20]. CD44 has also been identified as a marker of cancer stem cells (CSCs) in several solid tumors, as well as head and neck cancers, including oral squamous cell carcinomas and epithelial dysplasia [21][22][23][24]. The cancer stem cell model can explain the heterogeneity of cancer cells and facilitate the development of targeted treatment of head and neck squamous cell carcinomas [25].…”

Potential Immunohistochemical Biomarkers for Grading Oral Dysplasia: A Literature Review

“…CD44—cluster of differentiation 44—is a transmembrane glycoprotein [ 44 ]. Venkat Naga et al [ 45 ] used a cluster of differentiation 44 (CD44) antibody to assess the correlation between this marker and oral dysplasia grading. The authors compared four groups: control tissue, mild epithelial dysplasia, moderate epithelial dysplasia, and severe epithelial dysplasia.…”

Clinicopathological Correlation of Cyclooxygenase 2 Expression in Oral Submucous Fibrosis

“…[ 4 ] Over the recent past, attempts have been made to establish a potent diagnostic biomarker to explore the carcinogenesis underlying OSMF through IHC analysis. [ 5 ] The array of diagnostic markers studied using IHC in OSMF includes cell proliferation markers such as Ki 67 and cyclin D1,[ 5 6 ] tumor suppressor genes p53, p63, and p16,[ 6 7 ] transcription markers c-Jun, β-catenin, growth factor receptors c-Met and insulin-like growth factor II mRNA-binding protein 3 (IMP3),[ 5 ] epithelial to mesenchymal transition markers,[ 8 ] oncoproteins such as Bcl2,[ 9 ] apoptotic markers such as caspase 8, caspase 3,[ 10 11 ] cancer stem cell markers such as CD (cluster differentiation) 44,[ 12 ] pan endothelial markers associated with tumor angiogenesis CD34, CD105, growth factor markers such as basic fibroblast growth factor,[ 13 14 ] transforming growth factor-β1,TGF-β2,[ 15 ] cytokeratin markers such as CK 19,[ 16 ] and inflammatory markers such as cyclooxygenase (COX) 2. [ 17 ]…”