Clinical Significance of Altered Expression of β-Catenin and E-Cadherin in Oral Dysplasia and Cancer: Potential Link with ALCAM Expression

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Abstract
Perturbations in cell adhesion molecules are linked to alterations in cadherin-catenin complexes and likely play major roles in invasion and metastasis; their impact on early precancerous stages remains yet unknown. We showed ALCAM overexpression in early oral lesions and its cytoplasmic accumulation in oral squamous cell carcinoma (OSCC) to be a predictor of disease progression and poor prognosis. This study tested the hypothesis that alterations in E-cadherin and β -catenin expressions are early events in oral tumorigenesis, associated with disease prognosis, and correlate with perturbations in ALCAM expression. Expressions of E-cadherin and β-catenin were analyzed in the same cohort of 105 OSCCs, 76 oral lesions and 30 normal oral tissues by immunohistochemistry and correlated with clinicopathological parameters and prognosis. The effect of siRNA mediated ALCAM knockdown on E-cadherin and β -catenin was determined using western blot, confocal microscopy and RT-PCR analysis in oral cancer cells. Significant loss of membranous E-cadherin and β-catenin expression was observed from normal, hyperplasia, dysplasia to OSCCs (ptrend nuclear/cytoplasmic accumulation to be significant predictors for late clinical stage (pin vitro and in in vivo suggests that these dynamic changes in cell adhesion system may play pivotal role in oral cancer.

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