Nuclear Enolase-1/ MBP-1 expression and its association with the Wnt signaling in epithelial ovarian cancer.

BACKGROUND:Enolase-1, primarily known for its role in glucose metabolism, is overexpressed in various cancer entities. In contrast its alternative spliced nuclear isoform MBP-1 acts as a tumor suppressor. The aim of this study is to analyze the prognostic impact of Enolase-1/ MBP-1 and its functional significance in epithelial ovarian cancer (EOC). METHODS:By immunohistochemistry, Enolase-1 staining was examined in 156 EOC samples. Evaluation of Enolase-1 staining was conducted in the nucleus and the cytoplasm using the semi-quantitative immunoreactive score. Expression levels were correlated with clinical and pathological parameters as well as with overall survival to assess for prognostic impact. RESULTS:Cytoplasmic and nuclear Enolase-1 expression did not show a significant difference between the histological subtypes (p = 0.1). High nuclear Enolase-1/ MBP-1 staining negativly correlated with the tumor grading (p<0.001; Cc= -0.318). Cytoplasmic Enolase-1 did not correlate with clinicopathological data. Higher nuclear Enolase-1/ MBP-1 staining was detected in low-grade serous cancer cases compared to high-grade ones (median IRS 3 (range 0-8) vs. median IRS 2 (range 0-4), p<0.001). Nuclear Enolase-1/ MBP-1 expression correlated with the Wnt signaling markers membranous beta-catenin (p = 0.007; Cc=0.235), serine residue 9-phosphorylated glycogen synthase kinase 3 beta (p<0.001; Cc=0.341) and snail/slug (p = 0.004; Cc= -0.257). High nuclear Enolase-1/ MBP-1 expression was associated with improved overall survival (88.6 vs. 33.1 months, median; p = 0.013). CONCLUSION:Additional knowledge of Enolase-1/ MBP-1 as a biomarker and its interactions within the Wnt signaling pathway and epithelial-mesenchymal transition potentially improve the prognosis of therapeutic approaches in EOC.