Epidermal-Growth-Factor Receptors in Human Bladder Cancer: Comparison of Invasive and Superficial Tumours

Neal, D E; Bennett, MK; Rr, Hall; Marsh, Colin; Abel, PaulD.; Sainsbury, Jrc; Harris, A.L.

doi:10.1016/s0140-6736(85)91386-8

Cited by 540 publications

(241 citation statements)

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“…43,44 Furthermore, EGFR can 'crosstalk' with additional heterologous receptors activated by a variety of stimuli to amplify its biological activities. 40 In general, EGFR overexpression has been found to be associated with advanced tumor stage and poor prognosis in a number of human malignancies, such as carcinomas of the esophagus, 6 stomach, 45 colorectum, 16,46 bladder, 11 and breast. 10 Although inconclusive, these observations underscore the potential benefit of anti-EGFR therapy for patients with advanced diseases.…”

Section: Discussionmentioning

confidence: 99%

“…It is a member of the tyrosine kinase receptor family that also includes HER2 (erbB2), erbB3, and erbB4. 1 Studies have shown that EGFR is expressed in many types of normal tissue and overexpressed in common epithelial neoplasms such as carcinomas of the colorectum, 2-4 stomach, 4,5 esophagus, 6 lung, 7,8 pancreas, 9 breast, 10 bladder, 11 kidney 12 and head and neck. 13 It is believed that EGFR contributes to tumor development and progression through autocrine stimulation of cell proliferation, 14 and that tumors with increased EGFR expression levels generally bear a poorer prognosis.…”

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Expression of epidermal growth factor receptor in squamous cell carcinomas of the anal canal is independent of gene amplification

et al. 2006

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Immunohistochemical detection of expression of the epidermal growth factor receptor (EGFR) has been utilized to identify eligible patients with solid malignant tumors, including colorectal adenocarcinoma, for monoclonal antibody therapy (eg, cetuximab). The EGFR status in squamous cell carcinoma of the anal canal, an uncommon malignancy traditionally treated with chemoradiation, has not been well investigated. In this study, 38 primary squamous cell carcinomas of the anal canal were immunohistochemically examined for EGFR expression and analyzed by fluorescence in situ hybridization (FISH) for EGFR gene copy numbers. The results showed a variable degree of EGFR expression in 21 (55%) tumors, among which 13 (62%) cases exhibited a 2 þ to 3 þ staining pattern according to the Dako EGFR phamDx interpretation guide. There were no significant differences among tumors stratified by stage, degree of keratinization, or tissue block storage times. FISH analysis showed that none of the 34 cases with interpretable results had EGFR gene amplification. Increased gene copy numbers due to polysomy 7 were seen in seven of 18 (39%) cases that expressed EGFR protein and four of 16 (25%) cases that did not (P ¼ 0.3876). Ten (56%) tumors with positive EGFR staining showed a balanced disomy 7 pattern and one case with monosomy 7 exhibited strong EGFR expression (3 þ ). These results demonstrate that EGFR is overexpressed in more than one-half of the squamous cell carcinomas of the anal canal through mechanisms other than gene amplification. These observations may have important therapeutic implications since EGFR-based targeted therapies have shown promise for other malignant neoplasms.

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Section: Discussionmentioning

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confidence: 99%

Expression of epidermal growth factor receptor in squamous cell carcinomas of the anal canal is independent of gene amplification

et al. 2006

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“…Furthermore, Fitzpatrick et al (1984) observed that the highest quantities of EGF binding sites were expressed in tumours that lacked oestrogen receptors -a factor known to be associated with aneuploidy, a high S-phase content and poorer differentiation. Neal et al (1985) demonstrated that intense EGFR staining was related to poor differentiation of bladder cancers. The work of Veale et al (1987) was also confounded by a very small number of well differentiated squamous lung cancers and failed to demonstrate any significant relationship between EGFR staining and degree of differentiation.…”

Section: Immunohistochemistrymentioning

confidence: 99%

An immunohistochemical assessment of cellular proliferation markers in head and neck squamous cell cancers

Furlong²,

Cooke³

et al. 1990

Br J Cancer

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“…Many human cancers of epithelial origin express high numbers of EGF receptors and are stimulated by activation of the receptor via a transforming growth factor-α (TGF-α)/EGF receptor autocrine loop (Ozanne et al, 1986;Cowley et al, 1986;Ishitoya et al, 1989;Hendler and Ozanne, 1984). The increased receptor levels are associated with poor clinical prognosis in patients with cancers of the bladder (Neal et al, 1985), breast , and lung (Veale et al, 1987) and others. Blockade of EGF receptor as an approach for anticancer therapy has been extensively studied over the past decade (Fan and Mendelsohn, 1998).…”

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confidence: 99%

“…The increased receptor levels are associated with poor clinical prognosis in patients with cancers of the bladder (Neal et al, 1985), breast , and lung (Veale et al, 1987) and others. Blockade of EGF receptor as an approach for anticancer therapy has been extensively studied over the past decade (Fan and Mendelsohn, 1998).…”

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2000

Br J Cancer

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The receptor for epidermal growth factor (EGF) is a transmembrane glycoprotein with intrinsic tyrosine kinase activity (Ullrich and Schlessinger, 1990). Many human cancers of epithelial origin express high numbers of EGF receptors and are stimulated by activation of the receptor via a transforming growth factor-α (TGF-α)/EGF receptor autocrine loop (Ozanne et al, 1986;Cowley et al, 1986;Ishitoya et al, 1989;Hendler and Ozanne, 1984). The increased receptor levels are associated with poor clinical prognosis in patients with cancers of the bladder (Neal et al, 1985), breast , and lung (Veale et al, 1987) and others. Blockade of EGF receptor as an approach for anticancer therapy has been extensively studied over the past decade (Fan and Mendelsohn, 1998).Monoclonal antibody (mAb) 225 binds to EGF receptor with an affinity similar to that of the natural ligands EGF and TGF-α, competes with these natural ligands for receptor binding, and inhibits ligand-induced activation of the receptor tyrosine kinase (Sato et al, 1983;Gill et al, 1984). This antibody, along with other EGF receptor-blocking mAbs, inhibits the proliferation of a variety of cultured and xenografted tumour cell lines that are stimulated by the TGF-α/EGF receptor autocrine loop, including cell lines derived from cancers of the vulva (Fan et al, 1993a;1994), breast (Ennis et al, 1989), prostate (Peng et al, 1996;Hofer et al, 1991), ovary (Ye et al, 1999), bladder (Perrotte et al, 1999), kidney (Prewett et al, 1998), lung (Lee et al, 1992), colon (Karnes et al, 1992;Wu et al, 1996), brain (Wersall et al, 1997), and head and neck (Modjtahedi et al, 1993). It has been postulated that these antibodies inhibit tumour cell proliferation by an antibody-mediated interruption of the autocrine activation of EGF receptors in cancer cells (Van de Vijver et al, 1991;Fan et al, 1993b;Baselga et al, 1996). The antibody-mediated growth inhibition in most malignant cell lines has been attributed primarily to a reduced proliferation rate with an increased cell population in G1 phase of the cell cycle (Fan et al, 1997;Wu et al, 1996;Peng et al, 1996). In nonmalignant epithelial cells there was a prominent cytostatic effect with complete G1 arrest (Stampfer et al, 1993;Chou et al, 1999).DiFi colon cancer cells are unique in that exposure of these cells to mAb 225 resulted in not only G1 phase arrest of cell cycle, with a concomitant increase in the level of p27 Kip1 and a decrease in CDK activity, but also subsequent cell death through apoptosis (Wu et al, 1995;. When nude mice bearing well-established subcutaneous DiFi cell xenografts were treated with mAb 225, the tumour was completely eradicated, a result not normally seen with other cancer cells stimulated by the TGF-α/EGF receptor autocrine pathway (Masui et al, 1991). The EGF receptor gene in these cells was not found to be rearranged or genetically altered, but the gene was found to be amplified in the range of 60-80 copies per cell, which is approximately twice the copy number SummaryWe previously reported that e...

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Epidermal-Growth-Factor Receptors in Human Bladder Cancer: Comparison of Invasive and Superficial Tumours

Cited by 540 publications

References 10 publications

Expression of epidermal growth factor receptor in squamous cell carcinomas of the anal canal is independent of gene amplification

Expression of epidermal growth factor receptor in squamous cell carcinomas of the anal canal is independent of gene amplification

An immunohistochemical assessment of cellular proliferation markers in head and neck squamous cell cancers

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