Membrane localization of insulin receptor substrate-2 (IRS-2) is associated with decreased overall survival in breast cancer
AuthorsClark, Jennifer L
Kleer, Celina G
Shaw, Leslie M
Student AuthorsJennifer Clark
UMass Chan AffiliationsMorningside Graduate School of Biomedical Sciences
T.H. Chan School of Medicine
Document TypeJournal Article
MetadataShow full item record
AbstractRecent 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 < 0.001). When PR status and IRS-2 staining pattern were evaluated in combination, PR- tumors with IRS-2 at the membrane were associated with a significantly decreased OS when compared with all other combinations (P = 0.002). Evaluation of IRS-2 staining patterns could potentially be used to identify patients with PR- tumors who would most benefit from aggressive treatment.
SourceClark JL, Dresser K, Hsieh CC, Sabel M, Kleer CG, Khan A, Shaw LM. Membrane localization of insulin receptor substrate-2 (IRS-2) is associated with decreased overall survival in breast cancer. Breast Cancer Res Treat. 2011 Dec;130(3):759-72. doi: 10.1007/s10549-011-1353-1. Epub 2011 Jan 22. PMID: 21258861; PMCID: PMC3128655.
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/52039