Breast Cancer Research and Treatment

, Volume 130, Issue 3, pp 759–772

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

Authors

  • Jennifer L. Clark
    • Department of Cancer BiologyUniversity of Massachusetts Medical School
  • Karen Dresser
    • Department of PathologyUniversity of Massachusetts Medical School
  • Chung-Cheng Hsieh
    • Department of Cancer BiologyUniversity of Massachusetts Medical School
  • Michael Sabel
    • Department of SurgeryUniversity of Michigan Health System
  • Celina G. Kleer
    • Department of PathologyUniversity of Michigan Health System
  • Ashraf Khan
    • Department of PathologyUniversity of Massachusetts Medical School
    • Department of Cancer BiologyUniversity of Massachusetts Medical School
Preclinical study

DOI: 10.1007/s10549-011-1353-1

Cite this article as:
Clark, J.L., Dresser, K., Hsieh, C. et al. Breast Cancer Res Treat (2011) 130: 759. doi:10.1007/s10549-011-1353-1

Abstract

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.

Keywords

IRS proteinsBreast cancerProgesterone receptorIGF-1 receptor

Supplementary material

10549_2011_1353_MOESM1_ESM.pdf (34 kb)
Supplementary material 1 (PDF 34 kb)
10549_2011_1353_MOESM2_ESM.pdf (22 kb)
Supplemental Fig. 1 Analysis of IRS-2 diffuse staining pattern, progesterone receptor status, and overall survival. a, c, e Kaplan–Meier survival curves showing overall survival (OS) in Set 1 (a), Set 2 (c), and the Pooled Set (e) for patients with tumors exhibiting IRS-2 diffuse staining compared with non-diffuse IRS-2 staining. P values for both univariate and multivariate analyses are shown. b, c, f Kaplan–Meier survival curves showing OS in tumors from Set 1 (b), Set 2 (d), and the Pooled Set (f) as a function of both progesterone receptor (PR) and IRS-2 diffuse staining status. P values based on univariate analysis. (PDF 21 kb)
10549_2011_1353_MOESM3_ESM.pdf (22 kb)
Supplemental Fig. 2 Analysis of IRS-2 punctate staining pattern, progesterone receptor status, and overall survival. a, c, e Kaplan–Meier survival curves showing overall survival (OS) in Set 1 (a), Set 2 (c), and the Pooled Set (e) for patients with tumors exhibiting IRS-2 punctate staining compared with non-punctate IRS-2 staining. P values for both univariate and multivariate analyses are shown. b, c, f Kaplan–Meier survival curves showing OS in tumors from Set 1 (b), Set 2 (d), and the Pooled Set (f) as a function of both progesterone receptor (PR) and IRS-2 punctate staining status. P values based on univariate analysis. (PDF 21 kb)

Copyright information

© Springer Science+Business Media, LLC. 2011