Expression of E-cadherin and alpha-catenin in esophageal squamous cell carcinomas

T Setoyama, S Natsugoe, H Okumura, T Aikou

Department of Surgical Oncology and Digestive Surgery, Graduate School of Medicine, Kagoshima University, Kagoshima, Japan

AIM: E-cadherin regulates intercellular adhesion of the epithelial cells. Alpha-catenin is one of the E-cadherin-associated cytoplasmic proteins that forms a linkage to the cytoskeleton and regulates E-cadherin function. The reduced expression of cell adhesion molecules reportedly correlated with tumor growth and metastasis in gastrointestinal cancer. The purpose of the present study was to analyze the clinicopathologic findings according to the co-expression of E-cadherin and alfa-catenin in esophageal squamous cell cancer (ESCC). METHODS: We examined E-cadherin and alpha-catenin expressions by immunohistochemical staining in 203 patients with ESCC using monoclonal antibodies. The expressions of E-cadherin and alpfa-catenin in ESCC were compared to those of normal epithelial cells located distant area from the tumor. The intensity and pattern of E-cadherin and alfa-catenin expression in the cancer cells were divided into two groups: preserved expression (+) which indicated cells with the same expression as that of normal epithelium and reduced expression (-) which indicated cells with weak or negative expression compred with normal epithelium. RESULTS: The incidence of reduced expression of E-cadherin and alfa-catenin was 51% and 52%, respectively. When analyzing the relationship between E-cadherin expression and clinicopathologic factors, E-cadherin (-) was significantly related to the lymph node metastasis and TNM stage. Alfa-catenin (-) expression was also significantly associated with lymph node metastasis and stage grouping. A significant correlation was found between E-cadherin (-) and alpha-catenin (-) in the 80 patients (39%) (p<0.0001). When co-expression of E-cadherin and alfa-catenin was analyzed, Both E-cadherin (-) and alpha-catenin (-) expression was significantly associated with lymph node metastasis and TNM stage (p=0.0041 and 0.028, respectively). The frequency of hematogeneous and lymphatic metastasis in E-cadherin(-) and alpha – catenin(-) tumors was significantly higher than in E-cadherin(+)/alpha–catenin(+) tumors. In addition, the prognosis of patients with E-cadherin(-)/alpha-catenin(-) expression was significantly worse than that of patients with E-cadherin(+)/alpha-catenin(+) expression.(p<0.0001) CONCLUSIONS: The examination of co-expression of E-cadherin and alfa-catnin may be useful for predicting the lymph node metastasis and clinical outcome in patients with ESCC.

Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Nice, France; February 7 - 10, 2004; in poster session 893 (Molecular pathology).