PT  - JOURNAL ARTICLE
AU  - Sisci, Diego
AU  - Morelli, Catia
AU  - Garofalo, Cecilia
AU  - Romeo, Francesco
AU  - Morabito, Lucio
AU  - Casaburi, Filomena
AU  - Middea, Emilia
AU  - Cascio, Sandra
AU  - Brunelli, Elvira
AU  - Andò, Sebastiano
AU  - Surmacz, Eva
TI  - Expression of nuclear insulin receptor substrate 1 in breast cancer
AID  - 10.1136/jcp.2006.039107
DP  - 2007 Jun 01
TA  - Journal of Clinical Pathology
PG  - 633--641
VI  - 60
IP  - 6
4099  - http://jcp.bmj.com/content/60/6/633.short
4100  - http://jcp.bmj.com/content/60/6/633.full
SO  - J Clin Pathol2007 Jun 01; 60
AB  - 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.