Different patterns of beta-catenin expression in gastric carcinomas: relationship with clinicopathological parameters and prognostic outcome.

Objective: The cadherin-catenin complex is known to play a critical role in maintenance of cell adhesion. Additionally beta-catenin (beta-ct) can also take part in signal transduction and nuclear beta-ct expression could be correlated with poor prognosis in several malignancies. Since, in gastric cancer, this role of beta-ct is still uncertain, we investigated the expression pattern of beta-ct as well as the possible prognostic role.

Results: beta-catenin expression was immunohistochemically investigated in a retrospective series of 401 R0-resected gastric carcinomas. Out of these cases, 54 tumours (13.5%) revealed a preserved membranous beta-ct expression similar to that in normal gastric mucosa. In 80 tumours beta-ct expression was moderately reduced and in 117 tumours highly reduced. In 150 tumours (37.4%), no or only a weak membranous beta-ct expression was found. Additionally, in 53 tumours, a strong beta-ct expression could be observed in the cytoplasm with a simultaneous nuclear beta-ct immunoreactivity in 17 of these 53 tumours, while nine tumours only showed nuclear immunoreactivity without cytoplasmic staining. There were no significant correlations between the degree of membranous beta-ct expression or the different staining pattern (membranous vs. cytoplasmic/nuclear) and the grade of tumour differentiation, the histological tumour type according to Lauren, as well as with the prognostic parameters pT, pN category and vascular invasion. No associations could be found with tumour cell proliferation and the expression of E-cadherin, irrespectively of the different beta-ct staining pattern. Univariate analysis revealed no influence on survival, either for membranous or for cytoplasmic/nuclear beta-ct expression.

Conclusions: Our data on 401 tumours suggest that activation of the Wnt/beta-catenin signalling does also occur in a subset of gastric carcinomas. However, in gastric cancer, neither the presence of cytoplasmic/nuclear beta-ct expression nor the reduction or loss of membranous beta-ct expression is correlated with a specific histological tumour type, tumour progression or prognosis.