Nuclear IRS-1 predicts tamoxifen response in patients with early breast cancer

Insulin receptor substrate-1 (IRS-1) is a cytoplasmic scaffolding protein that is phosphorylated by insulin-like growth factor-I receptor and recruits downstream effectors. Recent evidence suggests that IRS-1 has a nuclear localization and function. Here we investigated whether nuclear and cytoplasm...

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Published in:Breast cancer research and treatment 2010-10, Vol.123 (3), p.651-660
Main Authors: Migliaccio, Ilenia, Wu, Meng-Fen, Gutierrez, Carolina, Malorni, Luca, Mohsin, Syed K., Allred, D. Craig, Hilsenbeck, Susan G., Osborne, C. Kent, Weiss, Heidi, Lee, Adrian V.
Format: Article
Language:English
Subjects:
Analysis
Antineoplastic Agents, Hormonal - therapeutic use
Biological and medical sciences
Biomarkers
Biomarkers, Tumor - analysis
Breast cancer
Breast Neoplasms - chemistry
Breast Neoplasms - drug therapy
Breast Neoplasms - mortality
Breast Neoplasms - pathology
Cancer patients
Cancer research
Cancer therapies
Cell Nucleus - chemistry
Disease-Free Survival
Endocrine therapy
Estrogen
Female
Gynecology. Andrology. Obstetrics
Humans
Immunohistochemistry
Insulin Receptor Substrate Proteins - analysis
Kaplan-Meier Estimate
Lymphatic Metastasis
Mammary gland diseases
Medical prognosis
Medical research
Medical sciences
Medicine
Medicine & Public Health
Medicine, Experimental
Middle Aged
Oncology
Preclinical Study
Progesterone
Proportional Hazards Models
Receptors, Estrogen - analysis
Receptors, Progesterone - analysis
Risk Assessment
Risk Factors
Survival Rate
Tamoxifen
Tamoxifen - therapeutic use
Taxation
Time Factors
Tissue Array Analysis
Treatment Outcome
Tumors
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Summary:Insulin receptor substrate-1 (IRS-1) is a cytoplasmic scaffolding protein that is phosphorylated by insulin-like growth factor-I receptor and recruits downstream effectors. Recent evidence suggests that IRS-1 has a nuclear localization and function. Here we investigated whether nuclear and cytoplasmic IRS-1 levels are associated with clinico-pathological characteristics and clinical outcome in breast cancer patients. Tissue microarrays from 1,097 patients with stage I–II breast cancer were stained by immunohistochemistry for IRS-1. Nuclear and cytoplasmic IRS-1 were scored separately according to the Allred score. Nuclear IRS-1 showed a positive association with estrogen receptor (ER) ( r  = 0.09, P  = 0.003) and progesterone receptor (PR) ( r  = 0.08, P  = 0.008) status and a negative correlation with lymph node involvement ( r  = −0.10, P  = 0.001). Cytoplasmic IRS-1 did not correlate with ER or PR but showed a positive correlation with tumor size ( r  = 0.10, P  = 0.001) and S-phase fraction ( r  = 0.16, P  
ISSN:0167-6806
1573-7217
DOI:10.1007/s10549-009-0632-6