Ezrin immunoreactivity in relation to survival in serous ovarian carcinoma patients

OBJECTIVE: Ezrin is a membrane-cytoskeleton linker protein, which regulates cell polarity and signaling. Increased ezrin expression in astrocytomas and uveal melanomas is correlated with unfavorable prognostic factors and reduced patient survival. We investigated ezrin IR in normal ovarian surface epithelium and serous ovarian carcinomas, and its relation with clinical parameters and patient outcome. METHODS: Tissue microarray blocks were constructed of all serous ovarian carcinoma tissue samples removed at a primary operation in Helsinki University Central Hospital between 1964 and 1999 and of healthy ovarian tissue samples. Ezrin expression was assessed by indirect immunohistochemistry using a monoclonal 3C12 ezrin antibody. Tissue samples (n = 440) were scored for the intensity of ezrin immunoreactivity, and the scores were compared with patient age, the stage and grade of disease, and disease outcome. RESULTS: Healthy ovarian epithelium showed strong polarized ezrin immunoreactivity. In serous ovarian carcinoma, the reactivity varied from strong (15.0% of samples) to moderate (57.3%) or weak/negative (27.7%) and the subcellular distribution was typically diffuse. Weak or negative expression of ezrin was associated with shorter survival (P = 0.027) but also with an advanced age of the patients (P = 0.0001), and a higher histological grade of the disease (P = 0.032). In Cox multivariate survival analysis, ezrin immunoreactivity had no independent effect on survival, when controlling for the stage and grade of the disease, and patient age. CONCLUSIONS: In contrast with astrocytomas and uveal melanomas, negative or weak ezrin immunoreactivity in serous ovarian carcinoma correlates with poor patient outcome.