The cadherin switch in ovarian high-grade serous carcinoma is associated with disease progression

Abstract

Ovarian high-grade serous carcinoma (HGSC) often has a poor prognosis because of late presentation, lack of sensitivity and specificity of screening modalities and the development of chemoresistance. New targeted therapy is required if survival in these cases is to improve. The profile of E-, P- and N-cadherins in ovarian cancer and its association with survival remain poorly understood. Reduced expression of E-cadherin in prostate cancer associated with increase in the expression of N- and P-cadherins is described as cadherin switch. We hypothesised that there is a switch in the expression of cadherins that regulates the behaviour of HGSC and possibly its outcome. To identify the stages of the cadherin switch in HGSC, we studied the immunoexpression of E-, P- and N-cadherins in a cohort of 177 cases of HGSC. High expression of P-cadherin was associated with poor patient survival and was significantly higher in stage 2 disease when compared with stage 1 and stage 3 disease (P = 0.033). In contrast, loss of E-cadherin was observed in stage 3 HGSC when compared with other stages (P = 0.050). E-, P- and N- cadherin expressions were significantly associated with disease outcome when assessed individually and in various combinations with an interesting profile. Our results indicate that the cadherin switch alters through progression of HGSC. The profile of combined cadherin expressions in association with survival raises expectations in targeted therapy.