Expression of growth factors, growth factor receptors and apoptosis related proteins in invasive breast cancer: relation to apoptotic rate

PURPOSE: To assess the relation between growth factors, growth-factor receptors, p53, bcl-2 and bax expression, and the rate of apoptosis in invasive breast cancer patients.

MATERIALS AND METHODS: Tumors from 45 patients were assessed by immunohistochemistry for expression patterns of five growth factors and their receptors; platelet-derived growth factor A chain (PDGF-AA) and PDGF-receptor alpha (PDGFalphaR), PDGF-BB and PDGFbetaR, transforming growth-factor alpha (TGFalpha) and its receptor-epidermal growth factor receptor (EGFR) and vascular-endothelial growth factor (VEGF) and its receptors vascular-endothelial growth factor receptor I (FLT-1) and vascular-endothelial growth factor receptor II (FLK-1/KDR), two growth-inhibiting factors; transforming-growth factor beta I (TGFbeta1) and TGFbeta2 and their receptor couple TGFbeta receptor I (TGFbetaR-I) and TGFbetaR-II, and basic-fibroblast growth factor (bFGF). Besides, the expression patterns of the bcl-2, bax and p53 gene products were investigated. Expression patterns were correlated to the number of apoptotic cells assessed by light microscopy.

RESULTS: PDGF-BB and bFGF showed a positive correlation with the AI (p = 0.006 and p = 0.030, respectively). EGFR expression was associated with a high number of apoptotic cells but did not reach significance (p = 0.10). None of the other individual growth factors, growth-inhibiting factors or receptors showed a significant relation with the AI. The presence of a possible auto- or paracrine loop of the TGFalpha/EGFR combination was associated with a high number of apoptotic cells but did not reach significance (p = 0.20). PDGF-AA, bFGF and EGFR expression showed a significant relation to p53 overexpression. TGFbeta2 expression showed an inverse correlation with p53 overexpression.

CONCLUSION: We found an association between several growth factors and growth-factor receptors with number of apoptotic cells. This underlines the importance of growth factors and their receptors not just in proliferation, but also, directly and/or indirectly, in regulating the rate of apoptosis in invasive breast cancer. Growth factors and their receptors may therefore be useful as targets of anti-cancer therapy by inducing apoptosis or increasing the sensitivity of cells for chemo- or hormonal therapy induced apoptosis.