EXPRESSION OF GROWTH-FACTORS, GROWTH-INHIBITING FACTORS, AND THEIR RECEPTORS IN INVASIVE BREAST-CANCER - II - CORRELATIONS WITH PROLIFERATION AND ANGIOGENESIS

Growth factors may play an important role in tumour growth and angioge nesis by their influence on tumour cell proliferation or their effect on neovascularization. The aim of the present study was to determine w hich of the growth factors, growth-inhibiting factors, and their recep tors investigated in a previous study are correlated with proliferatio n and angiogenesis in invasive breast cancer, with emphasis on the imp act of possible autocrine and paracrine loops. Five growth factors and their receptors: platelet-derived growth factor A chain (PDGF-AA) and PDGF alpha receptor (PDGF alpha R), PDGF-BB and PDGF beta receptor (P DGF beta R), transforming growth factor alpha (TGF alpha) and its rece ptor epidermal growth factor receptor (EGFR), and vascular endothelial growth factor (VEGF) and its receptors (Flt-1 and Flk-1/KDR; two grow th-inhibiting factors: transforming growth factor beta-1 (TGF beta 1) and TGF beta 2 and their receptor couple TGF beta R-I and TGF beta R-I I; and basic fibroblast growth factor (bFGF) were stained in 45 cases of invasive breast cancer by standard immunohistochemistry on frozen s ections. Staining in tumour cells, stromal cells, and endothelial cell s was scored as negative or positive. Proliferation was determined by assessment of the mitotic activity index (MAI) and the degree of angio genesis was measure by counting the number of microvessels (microvesse l density: MVD) in the most vascularized area of the tumour. bFGF and EGFR showed positive correlations with the MAI, while TGF beta 2 showe d a negative correlation. Expression of bFGF, TGF alpha, TGF beta 2, a nd EGFR correlated positively with the MVD. Co-expression of the TGF a lpha/EGFR growth factor/receptor combination showed a stronger correla tion with the MAI and the MVD than EGFR or TGF alpha alone, and the TG F beta 2/TGF beta R-I/TGF beta R-II combination showed a positive corr elation with the MVD. In conclusion, the expression of several growth factors, growth factor receptors, and growth-inhibiting factors showed correlations with the rate of proliferation and the degree of angioge nesis in invasive breast cancer. Some growth factor/receptor combinati ons showed stronger correlations with proliferation and angiogenesis t han the growth factor or receptor alone, pointing to the importance of possible auto-and paracrine loops for stimulation of proliferation an d angiogenesis by growth factors and their receptors. (C) 1998 John Wi ley & Sons, Ltd.