1: Adv Anat Pathol. 2005 Sep;12(5):271-3.


Clinical value of epidermal growth factor receptor expression in primary breast cancer.

Rampaul RS, Pinder SE, Nicholson RI, Gullick WJ, Robertson JF, Ellis IO.

Nottingham Breast Institute, University of Nottingham, Nottingham City Hospital, NHS Trust, Nottingham, UK. mszrsr@nottingham.ac.uk

EGFR expression in primary breast cancer has been extensively investigated for its prognostic and predictive value. However overall there is no consensus on its potential to guide such prognostication. This is largely because of the great heterogeneity in study designs and methods used to assay the EGFR protein. The impetus to standardize such studies is much needed as there are now several tyrosine kinase inhibitors directed against the EGF receptor and phase II trials are showing significant promise.

Publication Types:
Review

PMID: 16210923 [PubMed - indexed for MEDLINE]

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2: Eur J Cancer. 2005 Jul;41(10):1383-92.


Assessing epidermal growth factor receptor expression in tumours: what is the value of current test methods?

Dei Tos AP, Ellis I.

Department of Pathology, Regional Hospital of Treviso, Italy. apdeitos@ulss.tv.it

Over-expression of the epidermal growth factor receptor (EGFR) in tumours is associated with aggressive disease and poor clinical prognosis. In theory, the EGFR status of a tumour provides an indication of the likelihood of response to EGFR-targeted therapy. However, the clinical data do not support a relationship between EGFR expression and response to EGFR-targeted therapies cetuximab, gefitinib and erlotinib. Recently, patients who appear to lack EGFR expression have been shown to respond to cetuximab. Possible causes for this paradox include false negative results due to a lack of sensitivity in the detection system, heterogeneity of EGFR expression within the tumour and specific mutations that mediate response to the tyrosine kinase inhibitors. Immunohistochemistry is the most reliable assay for EGFR expression but its interpretation is confounded by the lack of non-standard techniques. Other approaches for measuring EGFR expression can be considered at best exploratory at this point. Further work is needed to identify how EGFR contributes to carcinogenic and metastatic processes. As tumours that appear to be EGFR negative can respond to cetuximab, there is some doubt as to the usefulness of immunohistochemistry as a screen to select patients for treatment. Histopathology will continue to be essential for unravelling the role of this enigmatic molecule and refining its status as a legitimate target in cancer therapy.

Publication Types:
Research Support, Non-U.S. Gov't
Review

PMID: 15919198 [PubMed - indexed for MEDLINE]

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3: J Reprod Dev. 2004 Jun;50(3):269-78.


Expression of epidermal growth factor receptor (EGF-R), vascular endothelial growth factor receptor (VEGF-R) and fibroblast growth factor receptor (FGF-R) systems in porcine oviduct and endometrium during the time of implantation.

Wollenhaupt K, Welter H, Einspanier R, Manabe N, Brüssow KP.

Research Institute for the Biology of Farm Animals, Dummerstorf, Germany.

The oviduct and uterus provide the environment for the establishment of pregnancy. Among others, growth factor systems are involved in functional signaling interactions at the pre- and peri-implantation maternal-conceptus interface in pigs. Distinct regulation of epidermal growth factor Receptor (EGF-R), vascular endothelial growth factor receptor (VEGF-R) and fibroblast growth factor receptor (FGF-R) systems and of bioactivation of EGF-R in porcine oviduct and endometrium during the estrous cycle, early pregnancy and during steroid replacement in ovariectomized gilts is summarized. Remarkable influences of ovarian steroids and EGF on the expression of specific markers of transcription and translation in these tissues are discussed. Known biological effects of the EGF, VEGF and FGF are related to cellular differentiation and angiogenesis. This suggests their involvement in the transformation of the endometrium into a decidua subsequently leading towards successful establishment of pregnancy. Peripheral steroids may exert their effects on epithelial cells both in a direct genomic manner or through mediators such as growth factors. The aim of our study was to draw specific attention to the paracrine regulation in the porcine endometrium especially during the implantation window.

Publication Types:
Review

PMID: 15226591 [PubMed - indexed for MEDLINE]

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4: Eur J Cancer. 2003 Jul;39(10):1348-54.


Epidermal growth factor receptor (EGFR) as a target in cancer therapy: understanding the role of receptor expression and other molecular determinants that could influence the response to anti-EGFR drugs.

Ciardiello F, Tortora G.

Cattedra di Oncologia Medica, Dipartimento Medico-Chirurgico di Internistica Clinica e Sperimentale, Seconda Università degli Studi di Napoli, Via S. Pansini 5, 8013 Naples, Italy. fortunatociardeillo@yahoo.com

The epidermal growth factor receptor (EGFR) is a rational target for cancer therapy because it is commonly expressed at a high level in a variety of solid tumours and it has been implicated in the control of cell survival, proliferation, metastasis and angiogenesis. However, despite evidence to suggest that EGFR expression is associated with a poor prognosis in some tumours (e.g. breast, head and neck carcinomas), the situation is by no means clear-cut. A number of issues are worthy of particular consideration, including how EGFR is measured and whether these assays are sensitive and reproducible, which mechanisms other than increased EGFR expression might cause the EGFR signalling drive to be increased, and the relationship, if any, between EGFR expression and the response to EGFR-targeted agents.

Publication Types:
Review

PMID: 12826036 [PubMed - indexed for MEDLINE]

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5: Gynecol Oncol. 2003 Jan;88(1 Pt 2):S43-6; discussion S52-5.


General keynote: expression of epidermal growth factor receptor family in transgenic mouse models of human breast cancer.

Muller WJ.

McMaster University.

Publication Types:
Review

PMID: 12586084 [PubMed - indexed for MEDLINE]

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6: Oral Oncol. 2003 Feb;39(2):138-43.


Epidermal growth factor receptor expression in ameloblastoma.

Vered M, Shohat I, Buchner A.

Department of Oral Pathology and Medicine, The Maurice and Gabriela Goldschleger School of Dental Medicine, Tel Aviv University, Tel Aviv, Israel.

Ameloblastoma is a locally aggressive tumor with possible lethal potential. Currently extensive surgery is the most acceptable treatment modality. AIM: To investigate the presence of EGFR in ameloblastoma in order to consider using newly developed anti-EGFR therapeutic agents in cases of unresectable tumors. The study consisted of 58 formalin-fixed, paraffin-embedded specimens of ameloblastoma that were immunohistochemically stained with a monoclonal anti-EGFR antibody (clone 31G7). Positive and negative controls determined specificity of the antibody. A staining score based on the staining intensity and the proportion of stained cells was established, ranging between 0 and 2. All specimens were EGFR positive; 8 (14%) exhibited the maximum score of 2 and 19 (33%) scored between 1 and 2. Since ameloblastomas are EGFR-positive tumors, anti-EGFR agents could be considered to reduce the size of large tumors and to treat unresectable tumors that are in close proximity to vital structures. Copyright 2002 Elsevier Science Ltd.

Publication Types:
Research Support, Non-U.S. Gov't
Review

PMID: 12509966 [PubMed - indexed for MEDLINE]

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7: Semin Oncol. 2002 Oct;29(5 Suppl 14):45-54.


Epidermal growth factor receptor expression and measurement in solid tumors.

Spaulding DC, Spaulding BO.

DakoCytomation, Carpinteria, CA 93013, USA.

The efficacies of targeted therapies for cancer treatment are dependent on the expression of the targeted molecule in the tumors of the treated patient population. Immunohistochemistry is an attractive assay format for determining protein expression in biopsies of solid tumors, and is widely used in pathology laboratories. An optimized immunohistochemistry assay for the epidermal growth factor receptor (EGFR) has been developed for the detection of EGFR in colorectal, head and neck, and other tumors that express EGFR, and the assay is being used in colorectal cancer trials of IMC-C225 to select patients for treatment. The specificity of the assay and the detection technology used will be described, along with other assay methodologies and applications for EGFR testing. Copyright 2002, Elsevier Science (USA). All rights reserved.

Publication Types:
Research Support, Non-U.S. Gov't
Review

PMID: 12422313 [PubMed - indexed for MEDLINE]

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8: Semin Oncol. 2002 Oct;29(5 Suppl 14):38-44.


Epidermal growth factor receptor expression, signal pathway, and inhibitors in non-small cell lung cancer.

Bunn PA Jr, Franklin W.

Departments of Medicine and Pathology, the University of Colorado Health Sciences Center, Denver, CO 80262, USA.

The majority of non-small cell lung cancers (NSCLCs) overexpress the epidermal growth factor receptor (EGFR). The EGFR is frequently overexpressed in preneoplastic bronchial lesions. Thus, EGFR is an excellent potential target for prevention and therapy. New agents developed to inhibit EGFR function include monoclonal antibodies to EGFR and small-molecule receptor tyrosine kinase inhibitors. Preclinical studies showed that both types of inhibitors blocked the in vitro growth of human NSCLC cell lines by inhibiting receptor phosphorylation and phosphorylation of downstream proteins including MAP kinases and AKT. Both types of inhibitors also slowed the growth of human NSCLC tumors in nude mice. Additive or synergistic growth inhibition resulted from the combination of either type of inhibitor with chemotherapy and/or radiotherapy. Clinical phase I and phase II trials showed that both types of inhibitors could be delivered safely, and serum concentrations equivalent to or higher than those required for in vitro activity were achieved. Skin rash was the dose-limiting toxicity with all inhibitors. The skin rash was dose related and reversible. Objective responses were observed in advanced-stage patients refractory to chemotherapy, though the responses were partial responses. Response rates appear higher when the inhibitors are combined with chemotherapy. The results of randomized trials comparing the use of chemotherapy alone with chemotherapy plus the inhibitors are eagerly awaited. Copyright 2002, Elsevier Science (USA). All rights reserved.

Publication Types:
Research Support, U.S. Gov't, P.H.S.
Review

PMID: 12422312 [PubMed - indexed for MEDLINE]

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9: Oncologist. 2002;7 Suppl 4:31-9.


Epidermal growth factor receptor dependence in human tumors: more than just expression?

Arteaga CL.

Department of Medicine, Vanderbilt-Ingram Comprehensive Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-6307, USA. Carlos.Arteaga@mcmail.vanderbilt.edu

The epidermal growth factor receptor (EGFR) is a rational target for antitumor strategies. EGFR signaling causes increased proliferation, decreased apoptosis, and enhanced tumor cell motility and neo-angiogenesis. The EGFR is expressed or highly expressed in a variety of human tumors of epithelial origin. ZD1839 (Iressa) is an orally active, selective EGFR tyrosine kinase inhibitor, which blocks signal transduction pathways implicated in proliferation and survival of cancer cells. The lack of a consistent method of evaluating levels of EGFR has caused a disparity in reports of the EGFR as a prognostic factor; however, for some tumors, EGFR is a strong prognostic indicator associated with more aggressive disease and reduced survival. So far, no clear association between EGFR levels and response to EGFR-targeted agents has been found. Preclinical studies with ZD1839 have noted a relationship between the two in some cases, but not others. EGFR signaling may be increased by a number of mechanisms in addition to high expression levels of EGFR, including receptor mutations, heterodimerization with other members of this receptor family such as HER2 (erbB2), increased expression of (autocrine/ paracrine) ligands, and alterations in molecules that control receptor signaling output. Each of these components could be assessed to give an indication of the magnitude of EGFR signal amplification. Evaluation of signaling components downstream from EGFR should provide information on the activation of the EGFR pathway. Until EGFR-based assays predictive of a response to receptor-targeted therapies are available, there is no clear justification for stratifying patients by EGFR status or excluding patients with low EGFR levels from trials with ZD1839 or other EGFR inhibitors.

Publication Types:
Review

PMID: 12202786 [PubMed - indexed for MEDLINE]

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10: In Vivo. 2000 Sep-Oct;14(5):587-96.


The coordinated functional expression of epidermal growth factor receptor and c-Met in colorectal carcinoma metastasis.

Herynk MH, Radinsky R.

Department of Cancer Biology, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.

The process of metastasis is a highly selective, nonrandom process resulting in the clonal selection of a population of cells that is able to detach from the primary tumor, invade and survive in the circulation, arrest, extravasate, and ultimately survive and proliferate in the secondary organ-specific site. Tumor cell interactions with the microenvironment can profoundly influence the survival and proliferation of the cell at a secondary site. The epidermal growth factor receptor (EGFR) and the hepatocyte growth factor receptor (c-Met) are two such receptor tyrosine kinases (RTKs) that have been causally implicated in colorectal carcinoma (CRC) progression and metastasis. Activation of these RTKs can stimulate a number of specific pathways directly effecting tumor cell migration, survival and proliferation. The aberrant regulation of the RTKs is often noted in advanced CRC and its' liver metastases and can significantly effect the metastatic phenotype of tumor cells.

Publication Types:
Review

PMID: 11125542 [PubMed - indexed for MEDLINE]

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11: Pediatr Nephrol. 1993 Oct;7(5):612-5.


Expression of the epidermal growth factor receptor in fetal kidney.

Goodyer PR, Cybulsky A, Goodyer C.

Division of Pediatric Nephrology, Montreal Children's Hospital, McGill University, Quebec, Canada.

Formation of the human kidney begins at the 6th week of fetal life when the first generations of nephrons are generated from foci of metanephric mesenchyme through contact with the branches of the ureteric bud. This process requires a proliferative burst which must be tightly regulated by local signals. In this report, we review the evidence that the epidermal growth factor receptor molecule is an important arbiter of these events.

Publication Types:
Review

PMID: 8251334 [PubMed - indexed for MEDLINE]

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12: Dig Dis. 1993;11(1):1-11.


Expression of epidermal growth factor, transforming growth factor alpha and their receptor in gastro-oesophageal diseases.

Jankowski J, Hopwood D, Wormsley KG.

Department of Medicine, University of Dundee, UK.

This article is a review of aspects of the expression of the regulatory peptides; epidermal growth factor (EGF), transforming growth factor alpha (TGF-alpha), and their receptor (EGF-R) in the epithelium of the human oesophagus and stomach in health and disease. It has become clear that TGF-alpha has increased expression in metaplastic, dysplastic and neoplastic tissue of the oesophagus compared with normal mucosa. The degree of abnormal expression becomes more marked as dysplasia increases. TGF-alpha expression is also increased in gastric neoplasias. EGF has a different pattern of expression, being decreased in oesophagitis and increased in gastritis. Although EGF is present in Barrett's oesophagitis, the expression of EGF does not discriminate between dysplastic and neoplastic epithelium. EGF-R is normally expressed on all gastro-intestinal epithelia, but its expression is increased in Barrett's epithelium, as well as in adenocarcinomas of the oesophagus and the stomach. The two peptides bind to their receptors on the mucosal cell membranes, and the co-expression of peptide and receptor is positively associated with varying degrees of cellular proliferation. The density of receptor expression may modulate the proliferative stimulus, leading to either mitogenic (regulated) or oncogenic (unregulated) growth.

Publication Types:
Review

PMID: 8443952 [PubMed - indexed for MEDLINE]

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13: Br Med Bull. 1991 Jan;47(1):87-98.


Prevalence of aberrant expression of the epidermal growth factor receptor in human cancers.

Gullick WJ.

ICRF Oncology Group, Royal Postgraduate Medical School, Hammersmith Hospital, London.

This chapter reviews briefly the prevalence of overexpression of the epidermal growth factor receptor in human cancers. In addition, it examines the mechanisms responsible for increased expression and its clinical significance.

Publication Types:
Review

PMID: 1863851 [PubMed - indexed for MEDLINE]

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14: Semin Cancer Biol. 1990 Oct;1(5):305-15.


Epidermal growth factor: receptor and ligand expression in human breast cancer.

Murphy LC, Dotzlaw H, Wong MS, Miller T, Mrockowski B, Gong Y, Murphy LJ.

Department of Biochemistry and Molecular Biology, University of Manitoba, Winnipeg, Canada.

The epidermal growth factor (EGF) gene is expressed by most human breast cancer cell lines as well as 83% of human breast cancers in vivo. Furthermore, EGF mRNA is detectable in normal human breast tissue. These data suggest that EGF may have a functional role in both normal and neoplastic human breast tissue. Expression of EGF was generally highest in steroid receptor positive human breast tumor biopsies and cell lines. EGF expression was increased by progestins in T-47D and ZR 75 human breast cancer cells. Furthermore, progestins specifically increased the level of TGF-alpha and EGF-receptor mRNA in T-47D cells. Under these same conditions progestins inhibit growth of the cells. Regulation of expression of EGF, TGF-alpha and the EGF-receptor is unlikely to be directly related to the mechanism of progestin induced growth inhibition in T47-D cells. T-47D-5 cells are more sensitive than T-47D cells to progestin and antiestrogen induced growth inhibition. T-47D-5 cells do not express EGF and contain very low levels of TGF-alpha mRNA. The higher level of EGF and TGF-alpha expression in T-47D cells may be one mechanism by which these cells decrease their sensitivity to growth inhibition by progestins and antiestrogens.

Publication Types:
Research Support, Non-U.S. Gov't
Review

PMID: 2103505 [PubMed - indexed for MEDLINE]

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15: Symp Soc Exp Biol. 1990;44:21-37.


Regulation of epidermal growth factor receptor expression and activation: a brief review.

Haley JD.

Department of Cancer Therapeutics, Oncogene Science Inc., Manhasset, NY 11030.

The epidermal growth factor receptor, a transmembrane protein tyrosine kinase, plays a crucial role in cellular signalling both in embryonic development and in adult tissues. By phosphorylation of substrate proteins on tyrosine, signals may be transmitted which result in gene expression, ion flux and mitogenesis to name but a few of the pleiotropic effects of receptor activation. The epidermal growth factor receptor is relatively well studied amongst an increasing family of tyrosine kinases and makes a good model system for studying structure-function relationships involved in signal transduction. Here, the structure-function relationships for cellular transformation by the EGF receptor proto-oncogene are reviewed as well as data pertaining to its overexpression in human tumors.

Publication Types:
Research Support, Non-U.S. Gov't
Review

PMID: 2130514 [PubMed - indexed for MEDLINE]