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Expression of nuclear insulin receptor substrate 1 in breast cancer
  1. Diego Sisci1,*,
  2. Catia Morelli1,*,
  3. Cecilia Garofalo1,
  4. Francesco Romeo2,
  5. Lucio Morabito2,
  6. Filomena Casaburi2,
  7. Emilia Middea1,
  8. Sandra Cascio3,
  9. Elvira Brunelli4,
  10. Sebastiano Andò5,
  11. Eva Surmacz3
  1. 1Department of Pharmaco-Biology, University of Calabria, Arcavacata di Rende, Italy
  2. 2Division of Anatomo-Pathology, Annunziata Hospital, Cosenza, Italy
  3. 3Sbarro Institute for Cancer Research and Molecular Medicine, Temple University, Philadelphia, Pennsylvania, USA
  4. 4Department of Ecology, University of Calabria, Arcavacata di Rende, Italy
  5. 5Department of Cellular Biology, University of Calabria, Arcavacata di Rende, Italy
  1. Correspondence to:
 Dr E Surmacz
 Sbarro Institute for Cancer Research and Molecular Medicine, College of Science and Technology, Temple University, 1900 N 12th St Rm 446, Philadelphia, PA 19122, USA; surmacz{at}


Background: Insulin receptor substrate 1 (IRS-1), a cytoplasmic protein transmitting signals from the insulin and insulin-like growth factor 1 receptors, has been implicated in breast cancer. Previously, it was reported that IRS-1 can be translocated to the nucleus and modulate oestrogen receptor α (ERα) activity in vitro. However, the expression of nuclear IRS-1 in breast cancer biopsy specimens has never been examined.

Aims: To assess whether nuclear IRS-1 is present in breast cancer and non-cancer mammary epithelium, and whether it correlates with other markers, especially ERα. Parallel studies were carried out for the expression of cytoplasmatic IRS-1.

Methods: IRS-1 and ERα expression was assessed by immunohistochemical analysis. Data were evaluated using Pearson’s correlation, linear regression and receiver operating characteristic analysis.

Results: Median nuclear IRS-1 expression was found to be low in normal mammary epithelial cells (1.6%) and high in benign tumours (20.5%), ductal grade 2 carcinoma (11.0%) and lobular carcinoma (∼30%). Median ERα expression in normal epithelium, benign tumours, ductal cancer grade 2 and 3, and lobular cancer grade 2 and 3 were 10.5, 20.5, 65.0, 0.0, 80 and 15%, respectively. Nuclear IRS-1 and ERα positively correlated in ductal cancer (p<0.001) and benign tumours (p<0.01), but were not associated in lobular cancer and normal mammary epithelium. In ductal carcinoma, both nuclear IRS-1 and ERα negatively correlated with tumour grade, size, mitotic index and lymph node involvement. Cytoplasmic IRS-1 was expressed in all specimens and positively correlated with ERα in ductal cancer.

Conclusions: A positive association between nuclear IRS-1 and ERα is a characteristic for ductal breast cancer and marks a more differentiated, non-metastatic phenotype.

  • Ab, antibody
  • ERα, oestrogen receptor α
  • IGF-I, insulin-like growth factor I
  • IGF-IR, insulin-like growth factor I receptor
  • IHC, immunohistochemical
  • IRS-1, insulin receptor substrate 1
  • PBS, phosphate-buffered saline
  • pN, lymph node status
  • pT, tumour size
  • ROC, receiver operating characteristic

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  • * These authors contributed equally to this work.

  • Published Online First 1 August 2006

  • Competing interests: None declared.