Expression of IGFBP-3 mRNA in breast cancer in relation to clinical phenotype
K McCarthy1, W Ogunkolade2, CA Laban1, S Khalaf2, SA Bustin3, R Carpenter1 & PJ Jenkins2
Background:Recent studies have linked low serum levels of IGFBP-3 with an increased risk of developing breast cancer.In addition to modulating IGF-I bioactivity, IGFBP-3 also exerts IGF-I independent pro-apoptotic effects. Our previous work has demonstrated that IGFBP-3 mRNA expression is significantly down regulated in breast tumours compared to normal breast tissue. It is uncertain, however, how this pattern of expression relates to the pathological and prognostic features of breast cancer. Tumours with estrogen receptor expression generally have an improved prognosis.
Aims: To compare the clinico-pathological features of breast tumours with low and high expression of IGFBP-3 expression.
Methods: Local Ethical Committee approval was obtained. Total RNA was extracted from 33 breast cancers. IGFBP-3 mRNA levels were quantified using real time RT-PCR and expressed as copy number/mcg total RNA. mRNA levels were correlated with tumour size, histological type, estrogen receptor(ER) status and presence of invasion into surrounding vasculature.
Results: IGFBP-3 mRNA was detected in all samples which was confirmed at a protein level using immunohistochemistry. mRNA levels were higher in the ER positive compared to the ER negative group(median copy number 1.71x10+8 vs 7.07x10+7respectively,p=0.03). They were also higher in those tumours with no vascular invasion compared to the those demonstrating vascular invasion(median copy number 1.79x10+8 vs 8.48x10+7, p=0.05). There was no difference in IGFBP-3 mRNA levels in tumours of different size, histological type and with lymph node metastases.
Conclusion: The increased expression of IGFBP-3 in tumours with better prognostic features (ER expression and lack of vascular invasion) is further evidence in suuport of its IGF independent effects. How it relates to the expression of IGF-1 remains to be determined.