Canonical and noncanonical Wnt pathway: A comparison among normal ovary, benign ovarian tumor and ovarian cancer

Abstract

The Wnt family is involved in tumorigenesis of several tissues. In ovarian cancer, the role played by Wnts and its pathways is not clearly defined. In order to analyze the canonical and noncanonical Wnt pathway in normal ovary, benign ovarian tumor and ovarian cancer, we evaluated the immunohistochemical expression of Wnt1, Frizzled-1 (FZD1), Wnt5a, Frizzled-5 (FZD5) and beta-catenin. Ovarian specimens were obtained from surgeries performed between 1993 and 2004. The patients were divided in three groups: group A, epithelial ovarian cancer (n=38); group B, benign epithelial neoplasia (n=28); and group C, normal ovaries (n=26). Immunoreactivity for Wnt1, FZD1, Wnt5a, FZD5 and beta-catenin was scored for each group. The proportion of Wnt1 positive women in group A (29.4%) was significantly higher than in group B (4.3%) and C (9.1%) (p=0.020). The proportion of FZD1 positive patients in group C (54.5%) was significantly lower than in group A (97.1%) and B (90.0%) (p<0.001). The proportion of Wnt5a positive women was significantly higher for group A (80.0%) compared to group B (25.0%) and C (27.3%) (p<0.001). The proportion of beta-catenin positive patients in group C (95.8%) was significantly higher than group B (52.4%) (p=0.004). Comparison of the survival curves in group A according to Wnt5a expression showed a significant difference between positive and negative patients, whereas the Wnt5a positive women showed worse results (p=0.050). Our findings suggest that the pathways related to Wnt5a have an important role in ovarian malignant neoplasia. Furthermore, Wnt5a was found to be a predictor of poor prognosis for ovarian cancer.