EXPRESSION OF GROWTH-FACTORS, GROWTH-INHIBITING FACTORS, AND THEIR RECEPTORS IN INVASIVE BREAST-CANCER - I - AN INVENTORY IN SEARCH OF AUTOCRINE AND PARACRINE LOOPS

The aim of the present study was to investigate which growth factors, receptors, and growth inhibiting factors are expressed in invasive bre ast cancer. Five (angiogenic) growth factors and their receptors: plat elet-derived growth factor A chain (PDCF-AA) and PDGF receptor alpha ( PDGF alpha R), PDGF-BB and PDGF beta receptor, transforming growth fac tor alpha (TGF alpha) and its receptor epidermal growth factor recepto r (EGFR), and vascular endothelial growth factor (VEGF) and its recept ors vascular endothelial growth factor receptor I (Flt-1) and vascular endothelial growth factor receptor II (Flk-1/KDR); two growth inhibit ing factors: transforming growth factor beta-1 (TGF beta 1) and TGF be ta 2) and their receptor couple transforming growth factor beta recept or I (TGF beta R-I) and TGF beta R-II; and basic fibroblast growth fac tor (bFGF), were stained by standard immunohistochemistry on frozen se ctions in 45 cases of invasive carcinoma of the breast. Staining was s cored as negative or positive in tumour epithelium, stroma, and blood vessels. TGF beta 1 and TGF beta 2 mere expressed in the tumour cells in 67 per cent and 76 per cent of cases, respectively,, whereas PDGF b eta R and TGF beta R-II were expressed in 0 per cent and 2 per cent, r espectively. The other factors showed variable expression in tumour ce lls. All factors were expressed in the stroma in most cases, except Fl t-1, Flk-1/KDR, TGF beta 2, and TGF beta R-II, which showed variable e xpression, and EGFR, which showed no expression. The endothelium was i n most cases positive for bFGF, PDGF-AA, PDGF-BB, VEGF, PDGF alpha R, PDGF beta R, and TGF beta 1 but TGF beta 2 was negative in most cases and TGF alpha, EGFR, Flt-1, Flk-1/KDR, TGF beta R-I, and TGF beta R-II were variably expressed. The most interesting possible auto/paracrine loops, as demonstrated on serial sections and by fluorescence double staining, mere the TGF alpha/EGFR, TGF beta s/TGF beta R, VEGF/Flt-1, and the VEGF/Flk-1 combinations. In conclusion, growth factors, growth inhibiting factors, and their receptors are frequently expressed in i nvasive breast cancer. Indications for some possible auto-and paracrin e loops have been found, which should encourage further study on the r ole of these factors in breast cancer proliferation and angiogenesis. (C) 1998 John Wiley & Sons, Ltd.