Membrane localization of insulin receptor substrate-2 (IRS-2) is associated with decreased overall survival in breast cancer

Recent studies have identified a role for insulin receptor substrate-2 (IRS-2) in promoting motility and metastasis in breast cancer. However, no published studies to date have examined IRS-2 expression in human breast tumors. We examined IRS-2 expression by immunohistochemistry (IHC) in normal brea...

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Bibliographic Details
Published in:Breast cancer research and treatment 2011-12, Vol.130 (3), p.759-772
Main Authors: Clark, Jennifer L., Dresser, Karen, Hsieh, Chung-Cheng, Sabel, Michael, Kleer, Celina G., Khan, Ashraf, Shaw, Leslie M.
Format: Article
Language:English
Subjects:
Adult
Aged
Biological and medical sciences
Breast cancer
Cancer research
Cancer therapies
Carcinoma, Ductal, Breast - metabolism
Carcinoma, Ductal, Breast - mortality
Carcinoma, Ductal, Breast - pathology
Cell Line, Tumor
Cell Membrane - metabolism
Female
Gynecology. Andrology. Obstetrics
Humans
Immunohistochemistry
Insulin
Insulin Receptor Substrate Proteins - metabolism
Kaplan-Meier Estimate
Mammary gland diseases
Mammary Glands, Human - metabolism
Mammary Glands, Human - pathology
Medical prognosis
Medical sciences
Medicine
Medicine & Public Health
Middle Aged
Neoplasm Grading
Neoplasm Staging
Oncology
Patient outcomes
Preclinical Study
Progesterone
Prognosis
Protein Transport
Proteins
Receptor, ErbB-2 - metabolism
Receptors, Estrogen - metabolism
Receptors, Progesterone - metabolism
Taxation
Tumors
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Summary:Recent studies have identified a role for insulin receptor substrate-2 (IRS-2) in promoting motility and metastasis in breast cancer. However, no published studies to date have examined IRS-2 expression in human breast tumors. We examined IRS-2 expression by immunohistochemistry (IHC) in normal breast tissue, benign breast lesions, and malignant breast tumors from the institutional pathology archives and a tumor microarray from a separate institution. Three distinct IRS-2 staining patterns were noted: diffusely cytoplasmic, punctate cytoplasmic, and localized to the cell membrane. The individual and pooled datasets were analyzed for associations of IRS-2 staining pattern with core clinical parameters and clinical outcomes. Univariate analysis revealed a trend toward decreased overall survival (OS) with IRS-2 membrane staining, and this association became significant upon multivariate analysis ( P  = 0.01). In progesterone receptor negative (PR−) tumors, in particular, IRS-2 staining at the membrane correlated with significantly worse OS than other IRS-2 staining patterns ( P  
ISSN:0167-6806
1573-7217
DOI:10.1007/s10549-011-1353-1