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This Article Full Text Full Text (PDF) All Versions of this Article: jcp.2006.039107v1 jcp.2006.039107v2 60/6/633    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this link to a friend Similar articles in this journal Similar articles in PubMed Add article to my folders Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sisci, D. Articles by Surmacz, E. Search for Related Content PubMed PubMed Citation Articles by Sisci, D. Articles by Surmacz, E. Pubmed/NCBI databases Medline Plus Health Information Breast Cancer

Expression of nuclear insulin receptor substrate 1 in breast cancer

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:
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.