Clinical significance of disordered beta-catenin expression pattern in human gastric cancers

BACKGROUND: Beta-catenin plays two distinct roles, in intercellular adhesion by E-cadherin, and in transcriptional activation via TCF/LEF. Theoretically, the former role is tumor-suppressive, while the latter is oncogenic. We investigated the involvement of beta-catenin in the histogenesis and clinical outcome of gastric cancers.METHODS: The expression pattern of beta-catenin was evaluated in stomach and lymph nodes from 82 patients with gastric cancer by immunohistochemistry and Western blot. Its association with E-cadherin expression and clinicopathological factors, including histological type and postoperative survival, was examined.RESULTS: Beta-catenin expression was classified into two patterns, normal (23.2%; 19 patients) and disordered (76.8%; 63 patients), the latter being subclassified as overexpressed (7.3%; 6 patients) and reduced (69.5%; 57 patients). A disordered beta-catenin expression pattern was significantly correlated with diffuse type adenocarcinoma and deep tumor infiltration ( P = 0.0154), but was not associated with lymph node metastasis ( P = 0.7877). E-cadherin was always expressed at the cell membrane, and disordered beta-catenin expression was significantly associated with reduced E-cadherin expression ( P < 0.0001). On univariate analysis, the beta-catenin pattern, as well as depth of invasion and lymph node metastasis, was associated with postoperative prognosis; however, only lymph node metastasis was an independent prognostic factor on multivariate analysis. Interestingly, different disordered patterns of beta-catenin expression, both overexpressed and reduced, were associated with E-cadherin reduction and poorer postoperative survival.CONCLUSION: Although disordered patterns of beta-catenin expression varied in gastric cancers, they were consistently associated with cancer progression.