title: High expression of insulin-like growth factor binding protein-2 messenger RNA in epithelial ovarian cancers produces elevated preoperative serum levels.
abstract: 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.
authors.affiliation: H. Lee Moffitt Cancer Center & Research Institute, University of South Florida, Tampa, 33612, USA. lancasjm@moffitt.usf.edu
authors.forename: J M
authors.initials: JM
authors.lastname: Lancaster
authors.forename: R A
authors.initials: RA
authors.lastname: Sayer
authors.forename: C
authors.initials: C
authors.lastname: Blanchette
authors.forename: B
authors.initials: B
authors.lastname: Calingaert
authors.forename: I
authors.initials: I
authors.lastname: Konidari
authors.forename: J
authors.initials: J
authors.lastname: Gray
authors.forename: J
authors.initials: J
authors.lastname: Schildkraut
authors.forename: D W
authors.initials: DW
authors.lastname: Schomberg
authors.forename: J R
authors.initials: JR
authors.lastname: Marks
authors.forename: A
authors.initials: A
authors.lastname: Berchuck
mesh_terms: D018262:Adenocarcinoma, Clear Cell / Q000097:blood / Q000235:genetics / Q000601:surgery; D002288:Adenocarcinoma, Mucinous / Q000097:blood / Q000235:genetics / Q000601:surgery; D014408:Biomarkers, Tumor / Q000097:blood*; D018394:CA-125 Antigen / Q000097:blood; D016022:Case-Control Studies; D018284:Cystadenocarcinoma, Serous / Q000097:blood / Q000235:genetics / Q000601:surgery; D016889:Endometrial Neoplasms / Q000097:blood / Q000235:genetics / Q000601:surgery; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D007124:Immunoenzyme Techniques; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000097:blood*; D009367:Neoplasm Staging; D009375:Neoplasms, Glandular and Epithelial / Q000097:blood* / Q000235:genetics / Q000601:surgery; D010048:Ovarian Cysts / Q000097:blood / Q000235:genetics; D010051:Ovarian Neoplasms / Q000097:blood* / Q000235:genetics / Q000601:surgery; D010053:Ovary / Q000473:pathology; D011230:Precancerous Conditions / Q000097:blood / Q000235:genetics / Q000601:surgery; D011300:Preoperative Care; D012333:RNA, Messenger / Q000097:blood* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D014408:Biomarkers, Tumor; D018394:CA-125 Antigen; D018971:Insulin-Like Growth Factor Binding Protein 2; D012333:RNA, Messenger