ASSESSMENT OF CK17 AND EPCAM EXPRESSION IN DIFFERENT GRADES OF ORAL SQUAMOUS CELL CARCINOMA

Abstract

CK17, being a component of cytoskeleton protein, is involved in the formation and maintenance of various skin appendages, regulation of protein synthesis and cell growth in injured stratified epithelia. Recently, new and unexpected roles of CK17 have been demonstrated in the cell growth and cell sizing of keratinocytes by its regulation of certain protein synthesis. In the shadow of these functions, and as CK17 is overexpressed in tumor tissue compared to normal oral mucosa, CK17 might be involved in the process of cancer development in OSCC. Therefore, among many CKs, CK17 seems to be a promising marker for diagnosis of OSCC. EpCAM, a calcium independent adhesion molecule, is a widely described tumor-associated antigen. Recent studies revealed overexpression or even de novo expression of EpCAM in epithelial cancers, that appears to be associated with variable roles of EpCAM in tumorigenesis that is not limited to cell adhesion but include diverse functions such as its role in signal transduction, regeneration of tissue, inhibiting differentiation, promoting proliferation and cell migration and invasion, and predicting poor prognosis and overall survival. This study was conducted to immunohistochemically investigate the expression of CK17 and EpCAM in different grades of OSCC, as well as to correlate both markers in different grades of OSCC if possible. Thirty-two formalin-fixed and paraffin-embedded specimens of oral squamous cell carcinoma with three different histopathological grades were used in this study. Thirteen cases were diagnosed as well-differentiated (well diff.) OSCC, nine diagnosed as moderately differentiated (mod. diff.) OSCC, and ten cases were diagnosed as poorly differentiated (poorly diff.) OSCC. Immunohistochemical staining using the biotin-streptavidin immunoperoxidase technique was performed with CK17 and EpCAM. The immunostained slides were examined by light microscopy and photographed. The photographs were then analyzed using image analysis software. For all cases, the area fraction of immunopositivity for four different microscopic fields was measured. The mean area fraction for each case was then calculated and used for statistical analysis. Immunohistochemical results of the present study revealed that mean area fraction of CK17 immunopositivity became lower as the grade increased [i.e. down-regulated from well diff. to poorly diff. OSCC] and same results were detected for EpCAM. The Tukey pair-wise test revealed a statistically significant difference between different grades of OSCC for CK17 and EpCAM (P-values < 0.001). In addition, statistical results of Pearson’s correlation analysis revealed a significant strong correlation between the CK17 and EpCAM in different grades of OSCC (R-value = 0.9131) (P-value = 0.0000). Based upon these data it could be concluded that expression of CK17 and EpCAM in OSCC might indicate their usefulness as a biological marker for neoplastic transformation and differentiation in OSCC. In addition, according to the difference in mean area fraction between the different grades of OSCC; CK17 and EpCAM could be used as a useful indicator that could help to stratify OSCC tumor grades. Since CK17 protein has been strongly expressed in well diff. OSCC; CK17 could be a precise candidate for early diagnosis of well diff. OSCC. On the other hand, the reduced EpCAM expression in poorly diff. OSCC; might strongly suggest it as a biomarker for prediction of the progression and the prognosis of OSCC patients. Thus, the overexpression of CK17 and EpCAM in combination can be used for early diagnosis and for predicting poor prognosis in patients with OSCC, and this may be more significant than a single marker.