ORIGINAL ARTICLE

Expression of nuclear insulin receptor substrate 1 in breast cancer

Diego Sisci^1,*, Catia Morelli^1,*, Cecilia Garofalo¹, Francesco Romeo², Lucio Morabito², Filomena Casaburi², Emilia Middea¹, Sandra Cascio³, Elvira Brunelli⁴, Sebastiano Andò⁵ and Eva Surmacz³

¹ Department of Pharmaco-Biology, University of Calabria, Arcavacata di Rende, Italy
² Division of Anatomo-Pathology, Annunziata Hospital, Cosenza, Italy
³ Sbarro Institute for Cancer Research and Molecular Medicine, Temple University, Philadelphia, Pennsylvania, USA
⁴ Department of Ecology, University of Calabria, Arcavacata di Rende, Italy
⁵ Department of Cellular Biology, University of Calabria, Arcavacata di Rende, Italy

Correspondence to:
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}temple.edu

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 (ER) 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 ER. Parallel studies were carried out for the expression of cytoplasmatic IRS-1.

Methods: IRS-1 and ER 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 ER 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 ER 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 ER negatively correlated with tumour grade, size, mitotic index and lymph node involvement. Cytoplasmic IRS-1 was expressed in all specimens and positively correlated with ER in ductal cancer.

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

Abbreviations: Ab, antibody; ER, oestrogen receptor ; 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

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Ravikumar, S., Perez-Liz, G., Del Vale, L., Soprano, D. R., Soprano, K. J. (2007). Insulin Receptor Substrate-1 Is an Important Mediator of Ovarian Cancer Cell Growth Suppression by All-trans Retinoic Acid. Cancer Res. 67: 9266-9275 [Abstract] [Full Text]