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

Abstract

Epithelial ovarian cancer is the leading cause of death among female genital malignancies. Reduced expression of the cell adhesion molecule E-cadherin was previously shown to be associated with adverse prognostic features. The role of the E-cadherin repressor Snail in ovarian cancer progression remains to be elucidated. We analysed formalin-fixed and paraffin-embedded specimens of 48 primary ovarian tumours and corresponding metastases for expression of E-cadherin and Snail by immunohistochemistry. We found a significant correlation between E-cadherin expression in primary cancers and their corresponding metastases (P<0.001). This correlation was found for Snail expression as well (P<0.001). There was a significant (P=0.008) association of reduced E-cadherin expression in primary ovarian cancer with shorter overall survival. Similarly, Snail expression in corresponding metastases (P=0.047) was associated with reduced overall survival of the patients. Additionally, the group of patients showing reduced E-cadherin and increased Snail immunoreactivity in primary tumours and corresponding metastases, respectively, had a significantly higher risk of death (P=0.002 and 0.022, respectively) when compared to the patient group with the reference expression profile E-cadherin positive and Snail negative. Taken together, the results of our study show that the E-cadherin repressor Snail is associated with lower overall survival of ovarian cancer patients.

Figure 1

(A, B) Consecutive immunostainings for E-cadherin and Snail of two ovarian cancer cases showing the primary tumours and the corresponding metastases. (A) An ovarian cancer case showing reduced E-cadherin immunostaining in the primary tumour (1+), while E-cadherin immunoreactivity is preserved in the corresponding metastasis (3+). Snail immunoreactivity is positive (3+) for both, primary tumour and metastasis (immunoperoxidase staining, × 200). (B) An ovarian cancer case showing preserved E-cadherin immunostaining (3+) in primary tumour and corresponding metastasis. Snail immunoreactivity is negative (0) in the primary tumour, whereas it is positive (1+) in the corresponding metastasis. Note that tumour-associated stromal cells also show nuclear staining for Snail (indicated by arrowheads) (immunoperoxidase staining, × 200). PT, primary tumour; MET, corresponding metastasis.

Figure 2

Kaplan–Meier survival curve for ovarian carcinoma patients according to E-cadherin immunoreactivity in primary ovarian cancers. Discontinuous line represents preserved E-cadherin immunoreactivity (3+). Continuous line represents reduced E-cadherin immunoreactivity (2+, 1+, and 0). Patients with reduced E-cadherin immunoreactivity had a significantly shorter overall survival (P=0.008).

Figure 3

Kaplan–Meier survival curve for ovarian carcinoma patients according to Snail immunoreactivity in metastases of ovarian cancer. Discontinuous line represents negative Snail immunoreactivity (0). Continuous line represents positive Snail immunoreactivity (1+, 2+, and 3+). Patients with positive Snail immunoreactivity had a significantly shorter overall survival (P=0.047).