High expression of insulin-like growth factor binding protein-2 messenger RNA in epithelial ovarian cancers produces...

The molecular etiology of epithelial ovarian cancer remains unclear. Using microarray expression analysis, we recently reported that expression of the insulin-like growth factor binding protein-2 (IGFBP-2) gene is elevated in advanced epithelial ovarian cancers. The aim of this study was to further delineate the role of IGFBP-2 in the pathoetiology of epithelial ovarian cancer and determine if elevated ovarian cancer IGFBP-2 gene expression is reflected in serum. Relative IGFBP-2 expression was measured using quantitative real-time polymerase chain reaction in 113 epithelial ovarian cancers and 6 normal ovarian surface epithelial samples. Preoperative serum IGFBP-2 levels were measured by radioimmunoassay in 84 women (42 ovarian cancers, 26 benign gynecological conditions, and 10 healthy female controls). Ovarian cancers demonstrated 38-fold higher mean IGFBP-2 expression than normal ovarian epithelium (P < 0.01). Serum IGFBP-2 levels were elevated in women with early- and advanced-stage ovarian cancer compared to controls and patients with benign gynecological conditions (P = 0.05 and P < 0.01, respectively). Epithelial ovarian cancers express high levels of IGFBP-2 relative to normal ovarian epithelium, and this is associated with elevated serum IGFBP-2 levels compared to both normal controls and patients with benign gynecological disease. Our findings provide further support that the insulin-like growth factor pathway plays a significant role in epithelial ovarian cancer pathogenesis. Further, IGFBP-2 may represent an additional serum biomarker with utility in detection and monitoring of epithelial ovarian cancer.