Prognostic significance of E-cadherin–catenin complex in epithelial ovarian cancer

Abstract

Objective: To clarify the prognostic role of E-cadherin and b-and c-catenins, and their relation to CD44 in epithelial ovarian carcinoma. Methods: The expression of E-cadherin and b-and c-catenins was analysed immunohistochemically in 305 primary epithelial ovarian cancers and 44 metastases, and related to CD44 expression, clinicopathological factors, and the patients' survival. Results: Reduced cell surface expression of E-cadherin, b-catenin, and c-catenin was particularly frequent in serous and endometrioid histological types. Reduced cell surface expression of E-cadherin and bcatenin was also associated with poor differentiation. Nuclear positivity of b-catenin was associated with high CD44 expression, endometrioid histology, and local stage of the tumour, whereas nuclear c-catenin expression was associated with serous histology and poor differentiation. In the univariate analysis, preserved cell surface b-catenin expression in the whole study material and nuclear expression of b-and c-catenins in the subgroup of endometrioid ovarian cancers were predictors of better 10 year disease related survival. Preserved cell surface expression of E-cadherin and b-catenin predicted favourable recurrence-free survival. These statistical significances were not retained in multivariate analysis. Conclusions:The correlation between nuclear b-catenin and CD44 indicates that b-catenin may regulate the transcription of CD44 in epithelial ovarian cancer. E-cadherin-catenin complex members are associated with the prognosis of patients with epithelial ovarian cancer, but these univariate associations were not strong enough to compete for significance with the traditional clinicopathological factors. C ell-cell adhesion determines tissue morphogenesis and regulates major cellular processes including motility, growth, differentiation, and survival. The E-cadherincatenin complex is necessary for the stabilisation of the adhesions and normal physiology of epithelial cells. Adhesion of neighbouring cells is mediated by cadherin, the cytoplasmic domain of which is connected to b-and c-catenins, which in turn bind to the actin cytoskeleton through acatenin. Disturbed adhesion often occurs in malignant tumours and may enhance the migration and proliferation of tumour cells, leading to invasion and metastasis.

The E-cadherin repressor Snail is associated with lower overall survival of ovarian cancer patients

“…The cell adhesion molecule E-cadherin has already been described to be involved in tumour dedifferentiation and poor recurrence-free survival in ovarian cancer (Imai et al, 2004;Voutilainen et al, 2006). We showed that reduced E-cadherin immunoreactivity in primary ovarian tumours was significantly (P ¼ 0.008) associated with shorter overall survival.…”

“…Occurrence of altered E-cadherin expression has been correlated with dedifferentiation, increased risk of local invasion and metastatic disease, and recurrence and poor prognosis in a variety of carcinomas, for example, breast, uterine cervix, or gastric carcinomas (Moll et al, 1993;Fujimoto et al, 1997;Jawhari et al, 1997;Jeffers et al, 1997;Huiping et al, 2001). Previous studies have shown that reduced expression of E-cadherin in ovarian cancer is associated with the invasive phenotype, advancing tumour stage, lower 5-year survival rate, and poor recurrence-free survival (Faleiro-Rodrigues et al, 2004;Imai et al, 2004;Marques et al, 2004;Voutilainen et al, 2006) but not much is known about the underlying mechanisms of E-cadherin downregulation.…”

Phenotypic plasticity of neoplastic ovarian epithelium: unique cadherin profiles in tumor progression

“…In more advanced, poorly differentiated carcinomas, both absent and persistent E-cadherin expression have been reported [16,18,51,59]. While complete loss of E-cadherin expression is uncommon, reduced E-cadherin staining is often detected in late stage carcinomas and in ascites-derived tumor cells [59,62,63]. Correspondingly, ascites cells may be more invasive than paired solid tumor cells from the same patient [60].…”

Actinin-4 expression in ovarian cancer: a novel prognostic indicator independent of clinical stage and histological type

“…Particular cell-to-cell adhesion molecules, especially E-cadherin and associated catenins, are thought to be involved in progression of ovarian cancer. [15][16][17][18][19] Indeed, downregulation or abnormal expression of E-cadherincatenin proteins has been reported to be associated with poor histologic differentiation of tumors, increased risk of peritoneal metastasis, and poor patient outcome in ovarian cancer as well as in various solid cancers at other primary sites. [19][20][21][22][23][24] Although, for disease progression, ovarian cancer cells should require cell motility besides loss of cellto-cell adhesion, the molecular backgrounds underlying this process is still unclear.…”