Expression of insulin receptor substrate 1 in primary breast cancer and lymph node metastases

Abstract

Background: Insulin receptor substrate 1 (IRS-1) transmits signals from the insulin-like growth factor I receptor (IGF-IR) and insulin receptor (IR) and has been associated with the pathogenesis of cancer. IRS-1 downregulation has been suggested to play a role in breast cancer progression, but no simultaneous assessments of IRS-1 expression in primary breast cancer and metastases have been performed.

Aims: To assess IRS-1 expression in primary and metastatic breast cancer.

Methods: IRS-1 expression was analysed by means of immunohistochemistry in 109 samples of primary breast cancer and in 42 matched primary and metastatic tumours. In addition, IRS-1 expression was correlated with selected clinicopathological features, including oestrogen receptor alpha (ERalpha) and proliferation marker Ki-67 status.

Results: Positive cytoplasmic IRS-1 immunostaining was found in 69.7% (76 of 109) and 76.2% (32 of 42) of the primary and metastatic tumours, respectively. Both IRS-1 positive and IRS-1 negative primary tumours produced IRS-1 positive and IRS-1 negative metastases. IRS-1 expression in primary tumours correlated with poorly differentiated (G3) breast cancer (p < 0.005) and with lymph node involvement (p <0.05). In the subgroup of ERalpha positive primary tumours, IRS-1 expression positively correlated with Ki-67 (p < 0.02, r = 0.351), but in the subgroup of ERalpha negative primary tumours there was a negative correlation (p < 0.03, r = -0.509). IRS-1 expression in lymph node metastases correlated with neither ERalpha nor Ki-67.

Conclusions: IRS-1 might be involved in breast cancer progression. Knowledge about differences between primary and metastatic tumours might help to understand mechanisms of breast cancer progression and lead to the development of more effective anticancer drugs.

Figure 1

Insulin receptor substrate 1 (IRS-1) expression in breast cancer. (A–C) Positive cytoplasmic and focally perinuclear IRS-1 immunostaining in primary tumour cancer cells. In (A), note the negative IRS-1 immunostaining in the mammary gland adjacent to the cancer. (D) Strong IRS-1 immunostaining in most of the cancer cells in a lymph node metastasis. Original magnification: A and B, ×100; C and D, ×200.