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


OBJECTIVE
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.
Koda
M
M
Department of Clinical Pathology, Medical University of Bialystok, Waszyngtona 13, 15-269 Bialystok, Poland.
Sulkowska
M
M
Kanczuga-Koda
L
L
Sulkowski
S
S
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism* / Q000473:pathology / Q000556:secondary*; D002454:Cell Differentiation; D049109:Cell Proliferation; D018450:Disease Progression; D047628:Estrogen Receptor alpha / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D055504:Insulin Receptor Substrate Proteins; D019394:Ki-67 Antigen / Q000378:metabolism; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*
D047628:Estrogen Receptor alpha; C526292:IRS1 protein, human; D055504:Insulin Receptor Substrate Proteins; D019394:Ki-67 Antigen; D009363:Neoplasm Proteins; D010750:Phosphoproteins