PMID- 16489075 OWN - NLM STAT- MEDLINE DCOM- 20060417 LR - 20151119 IS - 1078-0432 (Print) IS - 1078-0432 (Linking) VI - 12 IP - 4 DP - 2006 Feb 15 TI - The relationship of insulin-like growth factor-II, insulin-like growth factor binding protein-3, and estrogen receptor-alpha expression to disease progression in epithelial ovarian cancer. PG - 1208-14 AB - PURPOSE: The insulin-like growth factor (IGF) system plays important roles in cancer; blocking IGF signaling has been shown to have therapeutic effects on tumor growth. Many studies have focused on the effect of IGF-I, but few have addressed IGF-II. To assess the role of IGF-II in cancer, we analyzed IGF-II expression in ovarian cancer and examined its association with disease characteristics and prognosis. EXPERIMENTAL DESIGN: Included in the study were 215 patients with primary epithelial ovarian cancer. Fresh tumor specimens were collected during surgery, and the patients were followed for a median of 31 months. Total RNA was extracted from the tumor and analyzed for IGF-II, IGF binding protein 3 (IGFBP-3), and estrogen receptor-alpha expressions using quantitative reverse transcription PCR. Survival analysis was done to examine the associations of IGF-II with disease progression. RESULTS: IGF-II expression was found to be higher in tumors with poor prognosis; this included tumors with advanced stage, poor differentiation, serous histology, and large residual lesions. Patients with high IGF-II had elevated risk for disease progression and death, although the significance became less evident when the analysis was adjusted for clinical and pathologic variables. IGFBP-3 expression was higher in less aggressive tumors, but was not associated with disease progression. The expression of estrogen receptor-alpha had no effect on survival. CONCLUSION: This study found evidence that IGF-II expression is associated with disease progression, suggesting that IGF-II and IGF signaling are potential targets for ovarian cancer treatment. The study also indicates that IGF-II and IGFBP-3 have limited value in prognosis because of their strong associations with disease stage and tumor grade. FAU - Lu, Lingeng AU - Lu L AD - Department of Epidemiology and Public Health, Yale Cancer Center, Yale University School of Medicine, New Haven, Connecticut 06520-8034, USA. FAU - Katsaros, Dionyssios AU - Katsaros D FAU - Wiley, Andrew AU - Wiley A FAU - Rigault de la Longrais, Irene A AU - Rigault de la Longrais IA FAU - Risch, Harvey A AU - Risch HA FAU - Puopolo, Manuela AU - Puopolo M FAU - Yu, Herbert AU - Yu H LA - eng GR - R01AG21392/AG/NIA NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PL - United States TA - Clin Cancer Res JT - Clinical cancer research : an official journal of the American Association for Cancer Research JID - 9502500 RN - 0 (Biomarkers, Tumor) RN - 0 (Estrogen Receptor alpha) RN - 0 (Insulin-Like Growth Factor Binding Protein 3) RN - 0 (RNA, Neoplasm) RN - 67763-97-7 (Insulin-Like Growth Factor II) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Biomarkers, Tumor/*genetics MH - Disease Progression MH - Epithelial Cells/metabolism/pathology MH - Estrogen Receptor alpha/genetics MH - Female MH - *Gene Expression Regulation, Neoplastic MH - Humans MH - Insulin-Like Growth Factor Binding Protein 3/genetics MH - Insulin-Like Growth Factor II/genetics MH - Middle Aged MH - Neoplasm Staging MH - Ovarian Neoplasms/genetics/*pathology MH - RNA, Neoplasm/genetics/metabolism MH - Reverse Transcriptase Polymerase Chain Reaction MH - Survival Analysis EDAT- 2006/02/21 09:00 MHDA- 2006/04/18 09:00 CRDT- 2006/02/21 09:00 PHST- 2006/02/21 09:00 [pubmed] PHST- 2006/04/18 09:00 [medline] PHST- 2006/02/21 09:00 [entrez] AID - 12/4/1208 [pii] AID - 10.1158/1078-0432.CCR-05-1801 [doi] PST - ppublish SO - Clin Cancer Res. 2006 Feb 15;12(4):1208-14. doi: 10.1158/1078-0432.CCR-05-1801.