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Background β-catenin, a 92 kDa protein that binds to the cytoplasmic tail of E-cadherin, has an essential role in intercellular adhesion and signal transduction. Aberrant expression of β-catenin has been associated with progression and metastasis of various human cancers. The aim of this study was to elucidate the expression pattem of β-catenin in primary oral squamous cell carcinoma and examine the correlation between β-catenin expression and tumor differentiation, histological grade and lymph node status as well as its clinical significances.Methods Seventy-six patients with oral squamous cell carcinoma and sixteen metastatic lymph nodes were studied.The β-catenin expression was determined by immunohistochemical staining. The correlation with clinical, histological data was analyzed statistically.Results Normal oral epithelium showed strong β-catenin expression at the cell membrane, but no cytoplasmic or nuclear expression. Different degrees of reduced expression of β-catenin at the cell membrane were found in 54 cases with squamous cell carcinoma (71%). Cytoplasmic β-catenin expression was found in 17 tumors (22.4%). Three caseswere found with nuclear β-catenin expression. In sixteen lymph nodes with metastatic squamous cell carcinoma,negative β-catenin expression at the cell membrane was seen in 13 tumors (81.2%) and weak expression in 3 tumors (18.8%). Statistical analysis showed that there was an inverse correlation between β-catenin expression and lymph node status and histological grade of tumors.Conclusions Reduced β-catenin expression at the cell membrane is clearly associated with lymph node metastasis. A reduced expression of β-catenin may constitute a hallmark of aggressive biological behavior of squamous cell carcinoma.