Clinical implications of the EGF receptor/ligand system for tumor progression and survival in gastrointestinal carcinomas: evidence for new therapeutic options.

摘要: The epidermal growth factor (EGF) receptor and its various ligands (EGF, TGF-α, amphiregulin, heparin-binding (HB)-EGF, heregulin, betacellulin) seem to be involved in the regulation of intestinal mucosa might related development progression gastrointestinal tumors. However, few quantitative data investigating impact tumor-EGF levels carcinomas on tumor stage prognosis are available. Therefore, EGF receptors were quantitatively determined colorectal comparison adjacent normal by 125I[EGF]-binding studies. EGFR capacity was increased advanced invasive (Tl/2 vs. T3/4 tumors, p<0.001) UICC stages (UICC I II/III, p<0.001). These findings confirmed with 125 [I]EGF autoradiography performed frozen tissue slides analyzed laser densitometry (p=0.020). analysis immunohistochemistry antibodies directed against extracellular domain not correlated invasion or prognosis. mRNA-expression investigated using semiquantitative RT-PCR amplification specific primers. transcripts TGF- α, HB-EGF, amphiregulin) detected both mucosa, indicating that autocrine stimulation is mediated coexpression upregulation receptors. Survival cancer patients significantly reduced low/unchanged (mean survival±SD, 36.2±4.0 46.8±4.3 months; p=0.017). Further studies gastric have shown associated poor tumors localized distal from cardia. Several tyrosine kinase inhibitors recently entered clinical phase I–III studies, promisingantitumor effects several including cancer. benefit therapies specifically blocking EGFR-mediated signal transduction.