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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.

We investigated the expression and prognostic significance of matrix metalloproteinase (MMP) -7, its relation to b-catenin expression and clinicopathological factors in epithelial ovarian cancer. The expression of MMP-7 was analyzed immunohistochemically in a series of 284 primary epithelial ovarian cancers, their 36 metastases and 8 normal ovaries. In cancers with endometrioid histology, a high percentage area of MMP-7 expression and an intense MMP-7 signal was significantly associated with nuclear positivity of b-catenin in cancer cells (p 5 0.003, v 2 5 8.853 and p 5 0.030, v 2 5 4.713, respectively). In all tumors and nonendometrioid subgroup, a low percentage area of MMP-7 positive tumor cells was significantly correlated with a high histological grade of the tumor (p 5 0.003 and 0.005, respectively), in all tumors also with advanced stage of the tumor (p 5 0.002) and large primary residual tumor (p 5 0.005). A 10-year disease-related survival (DRS) was significantly better when the percentage area of MMP-7 expression in cancer cells was high, when compared to low (p 5 0.0008). A high percentage area of intense MMP-7 signal in cancer cells predicted a significantly more favorable DRS and recurrence-free survival (RFS) (p 5 0.0003 and 0.0052, respectively). In multivariate analysis, a high percentage area of intense MMP-7 signal in tumor cells was an independent prognostic factor, predicting favorable DRS and RFS. The present study showed that intense MMP-7 signal in tumor cells is an independent prognostic factor predicting better survival in epithelial ovarian cancer. ' 2006 Wiley-Liss, Inc.

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