This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints, Permissions and Rights Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Khosravi, J. Articles by Scorilas, A. Search for Related Content PubMed PubMed Citation Articles by Khosravi, J. Articles by Scorilas, A.

Insulin-Like Growth Factor I (IGF-I) and IGF-Binding Protein-3 in Benign Prostatic Hyperplasia and Prostate Cancer

Diagnostics Systems Laboratories, Inc. (J.K., A.D.), Toronto, Ontario, Canada M5G 1X5; Diagnostics Systems Laboratories, Inc. (J.M.), Webster, Texas 77598; and Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto (J.K., A.S.), Toronto, Ontario, Canada M5G 1L5

Address all correspondence and requests for reprints to: J. Khosravi, Ph.D., Diagnostics Systems Laboratories, Inc., Mount Sinai Hospital, Room 653, 600 University Avenue, Toronto, Ontario, Canada M5G 1X5. E-mail: jkhosravi{at}mtsinai.on.ca

In view of evidence indicating significant involvement of the insulin-like growth factor (IGF) system in the pathogenesis of prostate cancer, we measured serum IGF-I and IGF-binding protein-3 (IGFBP-3) in men with benign prostatic hyperplasia (BPH; n = 75) or prostatic carcinoma (CaP; n = 84). The age-matched patient populations were selected to have circulating prostate-specific antigen (PSA), the most reliable predictor of CaP, in the overlapping diagnostic gray zone range of approximately 4–10 µg/L. Of particular interest was investigation of intact, fragment, and total IGFBP-3 levels in relation to PSA, which is also a well established IGFBP-3 protease. Among the key findings were significantly higher IGF-I and intact IGFBP-3 levels in CaP vs. BPH (P < 0.001), whereas changes in fragment and total IGFBP-3 were statistically insignificant. As expected, total PSA levels were similar in the two groups of patients (P = 0.173), whereas free PSA levels were significantly lower in those with CaP (P < 0.001). IGF-I and IGFBP-3 (intact and total) correlated significantly (P = 0.024 to <0.001) and inversely (r = -0.26 to -0.35) with free PSA in BPH, but not in CaP, and no correlations were found in comparisons involving total PSA. Statistical analysis of the various markers and their combinations indicated enhanced performance of IGF-I/free PSA [receiver operating characteristics area under the curve (AUC) = 0.728] and intact IGFBP-3/free PSA (AUC = 0.737) ratios in discriminating between BPH and CaP compared with the currently used free/total PSA ratio (AUC = 0.689). Multivariate logistic regression models confirmed the observed relationships and identified IGF-I/free PSA and intact IGFBP-3/free PSA as independent factors in predicting the presence of CaP. We conclude that increases in IGF-I and intact IGFBP-3 levels are positively associated with the presence of CaP in this group of patients with low to moderately elevated PSA, and that their measurements in relation to PSA may help improve diagnostic discrimination between BPH and prostate cancer.

This article has been cited by other articles:

				T. R. Graham, H. E. Zhau, V. A. Odero-Marah, A. O. Osunkoya, K. S. Kimbro, M. Tighiouart, T. Liu, J. W. Simons, and R. M. O'Regan Insulin-like Growth Factor-I-Dependent Up-regulation of ZEB1 Drives Epithelial-to-Mesenchymal Transition in Human Prostate Cancer Cells Cancer Res., April 1, 2008; 68(7): 2479 - 2488. [Abstract] [Full Text] [PDF]

				Z. Wang, R. M. Luque, R. D. Kineman, V. H. Ray, K. T. Christov, D. D. Lantvit, T. Shirai, S. Hedayat, T. G. Unterman, M. C. Bosland, et al. Disruption of Growth Hormone Signaling Retards Prostate Carcinogenesis in the Probasin/TAg Rat Endocrinology, March 1, 2008; 149(3): 1366 - 1376. [Abstract] [Full Text] [PDF]

				C. Chen, R. Freeman, L. F. Voigt, A. Fitzpatrick, S. R. Plymate, and N. S. Weiss Prostate Cancer Risk in Relation to Selected Genetic Polymorphisms in Insulin-like Growth Factor-I, Insulin-like Growth Factor Binding Protein-3, and Insulin-like Growth Factor-I Receptor Cancer Epidemiol. Biomarkers Prev., December 1, 2006; 15(12): 2461 - 2466. [Abstract] [Full Text] [PDF]

				Z. Wang, G. S. Prins, K. T. Coschigano, J. J. Kopchick, J. E. Green, V. H. Ray, S. Hedayat, K. T. Christov, T. G. Unterman, and S. M. Swanson Disruption of Growth Hormone Signaling Retards Early Stages of Prostate Carcinogenesis in the C3(1)/T Antigen Mouse Endocrinology, December 1, 2005; 146(12): 5188 - 5196. [Abstract] [Full Text] [PDF]

				D. W. Voskuil, A. Vrieling, L. J. van't Veer, E. Kampman, and M. A. Rookus The Insulin-like Growth Factor System in Cancer Prevention: Potential of Dietary Intervention Strategies Cancer Epidemiol. Biomarkers Prev., January 1, 2005; 14(1): 195 - 203. [Abstract] [Full Text] [PDF]

				J. A. M. J. L. Janssen, M. F. Wildhagen, K. Ito, B. G. Blijenberg, R. H. N. van Schaik, M. J. Roobol, H. A. P. Pols, S. W. J. Lamberts, and F. H. Schroder Circulating Free Insulin-Like Growth Factor (IGF)-I , Total IGF-I, and IGF Binding Protein-3 Levels Do Not Predict the Future Risk to Develop Prostate Cancer: Results of a Case-Control Study Involving 201 Patients within a Population-Based Screening with a 4-Year Interval J. Clin. Endocrinol. Metab., September 1, 2004; 89(9): 4391 - 4396. [Abstract] [Full Text] [PDF]

				P. Stattin, S. Rinaldi, C. Biessy, U.-H. Stenman, G. Hallmans, and R. Kaaks High Levels of Circulating Insulin-Like Growth Factor-I Increase Prostate Cancer Risk: A Prospective Study in a Population-Based Nonscreened Cohort J. Clin. Oncol., August 1, 2004; 22(15): 3104 - 3112. [Abstract] [Full Text] [PDF]

				A. C. Baege, G. L. Disbrow, and R. Schlegel IGFBP-3, a Marker of Cellular Senescence, Is Overexpressed in Human Papillomavirus-Immortalized Cervical Cells and Enhances IGF-1-Induced Mitogenesis J. Virol., June 1, 2004; 78(11): 5720 - 5727. [Abstract] [Full Text] [PDF]

				A. HOEFLICH, M. M. WEBER, T. FISCH, S. NEDBAL, C. FOTTNER, M. W. ELMLINGER, R. WANKE, and E. WOLF Insulin-like growth factor binding protein 2 (IGFBP-2) separates hypertrophic and hyperplastic effects of growth hormone (GH)/IGF-I excess on adrenocortical cells in vivo FASEB J, November 1, 2002; 16(13): 1721 - 1731. [Abstract] [Full Text] [PDF]

				A. Calvo, N. Xiao, J. Kang, C. J. M. Best, I. Leiva, M. R. Emmert-Buck, C. Jorcyk, and J. E. Green Alterations in Gene Expression Profiles during Prostate Cancer Progression: Functional Correlations to Tumorigenicity and Down-Regulation of Selenoprotein-P in Mouse and Human Tumors Cancer Res., September 15, 2002; 62(18): 5325 - 5335. [Abstract] [Full Text] [PDF]

				L. H. Cazares, B.-L. Adam, M. D. Ward, S. Nasim, P. F. Schellhammer, O. J. Semmes, and G. L. Wright Jr. Normal, Benign, Preneoplastic, and Malignant Prostate Cells Have Distinct Protein Expression Profiles Resolved by Surface Enhanced Laser Desorption/Ionization Mass Spectrometry Clin. Cancer Res., August 1, 2002; 8(8): 2541 - 2552. [Abstract] [Full Text] [PDF]

				J. M. Chan, M. J. Stampfer, J. Ma, P. Gann, J. M. Gaziano, M. Pollak, and E. Giovannucci Insulin-Like Growth Factor-I (IGF-I) and IGF Binding Protein-3 as Predictors of Advanced-Stage Prostate Cancer J Natl Cancer Inst, July 17, 2002; 94(14): 1099 - 1106. [Abstract] [Full Text] [PDF]

				P. Stattin, U.-H. Stenman, E. Riboli, G. Hallmans, and R. Kaaks Ratios of IGF-I, IGF Binding Protein-3, and Prostate-Specific Antigen in Prostate Cancer Detection J. Clin. Endocrinol. Metab., December 1, 2001; 86(12): 5745 - 5748. [Abstract] [Full Text] [PDF]

				W Zumkeller IGFs and IGFBPs: surrogate markers for diagnosis and surveillance of tumour growth? Mol. Pathol., October 1, 2001; 54(5): 285 - 288. [Abstract] [Full Text] [PDF]