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Clinical Implications of the EGF Receptor/Ligand System for Tumor Progression and Survival in Gastrointestinal Carcinomas: Evidence for New Therapeutic Options

  • Conference paper
Molecular Staging of Cancer

Part of the book series: Recent Results in Cancer Research ((RECENTCANCER,volume 162))

Abstract

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

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Abbreviations

EGFR:

epidermal growth factor receptor

TGF-α:

transforming growth factor-alpha

HB-EGF:

heparin-binding epidermal growth factor

IHC:

immunohistochemistry

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  1. Department of Surgery, Klinikum Grosshadern, University of Munich, Marchioninistrasse 15, 81377, Munich, Germany

    Reinhard Kopp

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  1. Reinhard Kopp
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  2. Elisabeth Rothbauer
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  3. Maximilian Ruge
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  1. Dept. of Surgery, Klinikum Großhadern, Ludwig Maximilians Universität, Marchioninistr. 15, 81377, München, Germany

    Heike Allgayer  & Markus M. Heiss  & 

  2. Dept. of Surgery, Klinikum Großhadern, Ludwig Maximilians Universität, Marchioninistr. 15, 81377, München, Germany

    Friedrich W. Schildberg

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Kopp, R. et al. (2003). Clinical Implications of the EGF Receptor/Ligand System for Tumor Progression and Survival in Gastrointestinal Carcinomas: Evidence for New Therapeutic Options. In: Allgayer, H., Heiss, M.M., Schildberg, F.W. (eds) Molecular Staging of Cancer. Recent Results in Cancer Research, vol 162. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-59349-9_10

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  • DOI: https://doi.org/10.1007/978-3-642-59349-9_10

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