Serum Insulin-Like Growth Factors 1 and 2 and Insulin-Like Growth Factors Binding Proteins 1 and 3 in CIN and Invasive Cervical Cancer as Perspective Markers of Disease Progression

Cell proliferation and apoptosis are especially important for the formation of CIN and invasive cervical cancer. Insulin-like growth factors (IGF) 1 and 2, and several IGF-binding proteins (IGFBP) have been shown to play an important role in regulation of cell proliferation, differentiation and apoptosis. 64 patients with cervical neoplasia (22 CIN1-2, 7 microinvasive and 35 invasive cancer) and 16 women with no signs of cervical neoplasia were included in the study. The chosen stages present the important hallmarks of cancerogenesis: induction (CIN1-2), rupture of basal membrane (microinvasive cancer) and evident invasion (1B1 invasive cancer). Serum IGF-1, IGF-2, IGFPB-1, IGFPB-3 levels were measured by enzyme-linked immunoassays before treatment and IGFBP-1/IGFPB-3 rate was also assessed. In invasive cancer significant IGF-1, IGF-2, IGFPB-3 down-regulation as well as increase in IGFPB-1 level and IGFPB-1/IGFPB-3 rate was revealed. The only significant changes in microinvasive cancer were IGF-1 decrease and IGFPB-1 increase. Similar although not significant changes were seen in CIN1-2 patients thus confirming these proteins to be involved in cervical cancerogenesis. IGF family proteins might be perspective progression and «latent» invasion markers for patients with high-grade epithelial lesions. Lower IGF-1, IGF-2 and IGFPB-3 values as well as increased IGFPB-1 may reveal invasive cervical lesions. There is a need for further investigations to assess the critical IGF-1, IGF-2, IGFBP-3, IGFPB-1, IGFBP-1/IGFBP-3 endpoints associated with invasion.