Study On The Expression Of E-cadherin And Its Associated Proteins In Oral Squamous Cell Carcinomas

Objective: To study the expression of the epithelial adhesion molecule E cadherin (E-cad) and its associated proteins α catenin ( α-cat) and β catenin (β -cat) of 52 oral squamous cell carcinomas (OSCCs), especially at the invasive tumor front(ITF), as well as correlations with clinicopathological characteristics.Materials & Methods: The analysis was performed in 52 formalin-fixed, paraffin-embedded samples from patients with primary OSCCs who received operation treatment in Department of Oral and Maxillofacial Surgery, School of Stamotology, Wuhan University from June 1994 to December 2001. The whole tumor was graded using both WHO and IFG grading systems respectively by two experienced pathologists. The immunohistochemical expressions of E-cad, α -cat and β -cat were evaluated at the ITF and the other parts of the same tumor by comparing the intensity and cellular localization of immunostaining with those of the adjacent normal oral epithelium as an internal positive control, and correlations with clinicopathologic parameters were evaluated.Results:1. The expression of E-cad, α -cat and β -cat was consistently detected on the membrane of epithelium cells from the basal layer to the spinosum layer of adjacent normal oral epithelium, while the rate of reduced and loss expression of E-cad, α -cat and β -cat in OSCCs were 19.2% and 40.4%, 7.7% and 25.0%, 26.9% and 32.7% respectively. The expression of E-cad, α -cat and β -cat between adjacent normal oral epithelium and tumors was significant difference (P<0.01).2. As to WHO grading, E-cad, α -cat and β-cat expression was significantly higher in Ⅰ + Ⅱ grade than that in Ⅲ grade (P<0.05). For E-cad expression, there was no significant difference in different clinical stage, so were a -cat and P -cat expression.3. E-cad, α -cat and β -cat expression at the ITF was lower than that at the centre of OSCCs, the difference was statistically significant (P<0.01). In someOSCCs, ￡ -cat expression at the ITF was observed in cytoplasm of cancer cells, which is different from the usual staining pattern. A significant correlation was found between the expression of E-cad, a catenin at the ITF and the complete score of IFG (rE=-0.451, P<0.001; ra=-0.453, P<0.001), and tumor thickness (rE=-0.310, P<0.05; ra=-0.403, P<0.01). The expression of 8 catenin at the ITF was nonsignificantly correlated with the complete IFG score and tumor thickness(data not shown).4. The correlation among E-cad, a-cat and 6-cat were significant in OSCCs. Coexpression of E-cad/cat complex was observed in 63.5% as a whole and 73.1% at the ITF; and was significantly correlated with WHO grading (r=-0.341, /)=0.013<0.05) and IFG grading (r=-0.388, P=0.005<0.01) respectively.5. Survival in patients showing reduced (25%-75%) and loss (<25%) expressions of a-cat at the ITF were significantly shorter than in patients showing preserved (^75%) expressions (log rank P<0.01). The complete IFG score (P<0.01), the tumor thickness (P<0.01), the expression of a -cat at the ITF (P<0.01) and the WHO grading (P<0.05) were significant in the univariate cox analysis. The multivariate cox linear logistic regression model showed that the complete IFG score, the tumor thickness were significantly independed prognostic factors for overall survival and cumulative survival for OSCCs (P<0.01). Gender, age, the expression of E-cad and P -cat at the ITF were no statistical significance(data not shown).Conclusions: E-cad, a -cat and P -cat were reduced in OSCCs. The expression of E-cad/cat complex was correlated with tumor differentiation. The expression of E-cad, a -cat and P -cat at the ITF were significantly lower than that of other parts. The expression of E-cad and a -cat at the ITF was significantly correlated with the complete IFG score; and they were reduced or lost in some deeper tumor. Moreover, a -cat at the ITF could predict the high- and low-risk groups of tumors; and its expression at the ITF could be of value of adding prognostic value and treatment planning for OSCCs.