Membrane localization of insulin receptor substrate-2 (IRS-2) is associated with decreased overall survival in breast cancer
- نوع فایل : کتاب
- زبان : انگلیسی
- مؤلف : Jennifer L. Clark Karen Dresser Chung-Cheng Hsieh Michael Sabel Celina G. Kleer Ashraf Khan Leslie M. Shaw
- چاپ و سال / کشور: 2011
Description
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\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.
Breast Cancer Res Treat DOI 10.1007/s10549-011-1353-1 Received: 30 September 2010 / Accepted: 10 January 2011
