Characterization of the expression and activation of the epidermal growth factor receptor in squamous cell carcinoma of the skin
- 28 November 2006
- journal article
- Published by Oxford University Press (OUP) in British Journal of Dermatology
- Vol. 156 (1) , 92-98
- https://doi.org/10.1111/j.1365-2133.2006.07603.x
Abstract
Background Locally advanced skin cancers including squamous cell carcinoma (SCC) of the skin are increasing in incidence. Patients are often elderly with significant comorbidities and therapy can be difficult. New targeted therapies, such as treatment directed at the epidermal growth factor receptor (EGFR), may be effective and less toxic in these patients. However, before designing appropriate clinical trials it is necessary to characterize the expression and activation of targets such as the EGFR to evaluate the rationale of using EGFR inhibitors (EGFRIs) in the treatment of this type of cancer. Objectives To characterize the expression and activation by phosphorylation of EGFR in SCC of the skin by quantitative Western blotting using the LiCor immunofluorescence detection system with validation by immunohistochemistry. Secondary objectives were to evaluate downstream targets of EGFR expression and activation in SCC of the skin and to examine the associations between EGFR, pathological features and clinical behaviour of these tumours. Methods Twenty‐one mainly locally advanced skin SCCs collected in our institution and stored in our tissue bank over a 4‐year period were used for the study. Results Nine of 21 (43%) tumours expressed EGFR above background. Of those nine, five expressed phosphorylated EGFR. There was no correlation with downstream activation of canonical signalling pathways, pathological features or clinical behaviour. Conclusions EGFR is expressed in a minority of tumours and then is not always activated. These results show that, before designing a trial with a targeted agent such as an EGFRI in SCC of the skin, it is important to verify the presence of the appropriate target to maximize the best outcome.Keywords
This publication has 19 references indexed in Scilit:
- Randomized Phase II Trial of the Efficacy and Safety of Trastuzumab Combined With Docetaxel in Patients With Human Epidermal Growth Factor Receptor 2–Positive Metastatic Breast Cancer Administered As First-Line Treatment: The M77001 Study GroupJournal of Clinical Oncology, 2005
- Phase III evaluation of radiation with and without cetuximab for locoregionally advanced head and neck cancerInternational Journal of Radiation Oncology*Biology*Physics, 2004
- Status of Epidermal Growth Factor Receptor Antagonists in the Biology and Treatment of CancerJournal of Clinical Oncology, 2003
- EGFR blockade with ZD1839 (“Iressa”) potentiates the antitumor effects of single and multiple fractions of ionizing radiation in human A431 squamous cell carcinomaInternational Journal of Radiation Oncology*Biology*Physics, 2003
- Pharmacodynamic Studies of the Epidermal Growth Factor Receptor Inhibitor ZD1839 in Skin From Cancer Patients: Histopathologic and Molecular Consequences of Receptor InhibitionJournal of Clinical Oncology, 2002
- Use of Chemotherapy plus a Monoclonal Antibody against HER2 for Metastatic Breast Cancer That Overexpresses HER2New England Journal of Medicine, 2001
- Levels of TGF-α and EGFR Protein in Head and Neck Squamous Cell Carcinoma and Patient SurvivalJNCI Journal of the National Cancer Institute, 1998
- Epidermal growth factor receptors in human epidermal tumoursBritish Journal of Dermatology, 1990
- Association of EGF receptor expression with proliferating cells and of ras p21 expression with differentiating cells in various skin tumoursBritish Journal of Dermatology, 1990
- Comparison of Epidermal Growth Factor Binding and Receptor Distribution in Normal Human Epidermis and Epidermal AppendagesJournal of Investigative Dermatology, 1984