Japanese Journal of Clinical Oncology Advance Access published online on August 3, 2007
Japanese Journal of Clinical Oncology, doi:10.1093/jjco/hym066
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© 2007 Foundation for Promotion of Cancer Research
Prognostic Significance of Insulin-like Growth Factor Binding Protein (IGFBP)-4 and IGFBP-5 Expression in Breast Cancer
1 Oncology and Immunology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
2 Department of Molecular Medical Technology, Tohoku University, Sendai
3 Breast and Endocrine Surgery, Kumamoto University, Kumamoto, Japan
For reprints and all correspondence: Hiroko Yamashita, Oncology and Immunology, Nagoya City University Graduate School of Medical Sciences, Kawasumi 1, Mizuho-ku, Nagoya 467-8601, Japan. E-mail: hirokoy{at}med.nagoya-cu.ac.jp
Received December 10, 2006; accepted March 17, 2007
Background: Expression of estrogen-regulated genes has been considered as potential predictive markers for endocrine therapy. We focused on two insulin-like growth factor binding proteins (IGFBPs): IGFBP-4, which is an early-responsive estrogen-induced gene, and IGFBP-5, which is an estrogen-repressed gene. Investigation of IGFBP-4 and IGFBP-5 expression would provide important information for predicting prognosis and endocrine responsiveness.
Methods: The levels of IGFBP-4 and IGFBP-5 mRNA expression in 162 human breast cancer tissues were analyzed using quantitative real-time reverse transcriptase-PCR. The association between IGFBP-4 and IGFBP-5 expression and clinicopathological factors was then analyzed.
Results: The levels of IGFBP-4 and IGFBP-5 mRNA expression were positively correlated with estrogen receptor (ER) and progesterone receptor (PgR) status and were negatively correlated with HER2 overexpression. Patients with a high level of IGFBP-4 mRNA expression had better disease-free and overall survival than those with a low expression. Multivariate analysis showed that IGFBP-4 mRNA expression is an independent prognostic factor for disease-free survival. When analyzed in 116 patients with ER-positive breast cancer, patients whose tumor expressed higher levels of IGFBP-4 mRNA or lower levels of IGFBP-5 mRNA had better disease-free survival.
Conclusion: IGFBP-4 mRNA expression was an independent prognostic factor in breast cancer, and patients with ER-positive breast cancer whose tumor expressed higher levels of IGFBP-4 and lower levels of IGFBP-5 had a better prognosis than those without such findings.
Key Words: breast cancer • IGFBP-4 • IGFBP-5 • prognosis