Analysis of growth regulation in cancer containing breasts

Despite extensive research, the pathways of breast cancer development remains largely unknown. Identification of key alterations, particularly at early stages of the disease, are central to elucidating the development of the disease.;The hypothesis is that pre-cancerous breast which may or may not appear histologically normal has a defect in growth regulation. Analysis of growth regulation in breasts in which a cancer has developed could identify markers present in morphologically normal breast tissue, reflecting early stages of breast cancer development.;209 age matched cases [104 non-involved tissues from cancer-containing breasts (NTCCB's) and 105 normal/benign tissues as a control group] were characterised in terms of cell proliferation and apoptosis by MIB-1/histone mRNA and Tdt-mediated bio-dUTP Nick End Labelling (TUNEL) measurements respectively. These analyses demonstrated a significant reduction in apoptosis and lower apoptosis and lower apoptotic:proliferative indices ratios in the NTCCB's compared with controls. No significant difference in proliferation was obtained between the two groups.;Epidermal growth factor receptor (EGFR), insulin growth factors I and II (IGF), and insulin growth factor binding protien3 (IGFBP-3) expression was determined in some cases to investigate their possible roles in aberrant growth regulatory pathways of breast cancer development. EGFR immunohistochemistry and in situ hybridisation (ISH) and IGF-I immunohistochemistry and RT-PCR identified lower level of expression in NTCCB's compared with controls.;IGF-II immunohistochemsitry demonstrated an increased staining in the NTCCB compared with controls but there was decreased mRNA expression as determined by ISH. No differences were observed for IGFBP-3 expression between both groups.;Interestingly, IGF-I/II mRNA was confined to stomal cells suggesting a paracrine function.;Differences have been identified in cancer-containing breasts regarding reduced apoptosis and altered EGFR and IGF expression which indicate that there is altered growth regulation in morphologically normal breast which may contribute to the development of breast cancer.