Is immunohistochemical epidermal growth factor receptor expression overestimated as a prognostic factor in head-neck squamous cell carcinoma? A retrospective analysis based on a tissue microarray of 365 carcinomas (original) (raw)
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Human pathology, 2008
There is currently no prognostic tool that reliably predicts the risk of metastasis in cutaneous squamous cell carcinoma, most of which occur in the head and neck region. Epidermal growth factor receptor has received much interest in recent years with the advent of epidermal growth factor receptor-targeted molecular therapy in clinical oncology. We investigate the role of epidermal growth factor receptor as a biomarker for head and neck cutaneous squamous cell carcinoma. Using immunohistochemistry and fluorescence in situ hybridization, we assessed the epidermal growth factor receptor protein expression and gene copy in 3 groups of head and neck cutaneous squamous cell carcinoma: primary lesions not associated with metastasis (P), primary lesions associated with subsequent metastasis (PM), and metastatic nodal disease (M). Epidermal growth factor receptor overexpression was detected in 36% and 79% of P and PM cases, respectively. Epidermal growth factor receptor overexpression was s...
Head & Neck, 1991
Epidermal growth factor (EGF) stimulates the growth of several types of epithelial tissues and possesses a strong mitogenic activity that is mediated through its cell surface receptor (EGFR). The aim of this study was to characterize EGFR and measure its levels in head and neck tumors biopsies (70 patients); use of a simplified competition technique with a radiolabeled ligand allowed evaluation of functional EGFR. Five samples (4 tumors and 1 control) were used to characterize EGF binding. Graphic representation identified a single family of binding sites. Kd values revealed high affinity for EGF binding: mean Kd, 0.156 f 0.1 08 nM (0.095-0.347 nM). EGF-binding characteristics (Kd) tion was found between EGFR levels and tumor size and stage. Controls exhibited a trend toward higher EGFR levels in elevated sizes and stages. According to a cutoff EGFR value of 100 frnol/rng protein, which separated all controls from tumors, EGFR-positive tumors (>lo0 fmol/mg protein) had a greater probability of complete response to chemotherapy than EGFRnegative tumors; other tumor characteristics, such as the degree of tumoral differentiation, tumor size, or stage, were unable to operate such a discrimination in the response to chemotherapy. EGFR may thus be an interesting biological marker for head and neck cancer. HEAD & NECK 1991;13:132-139 were similar in nontumoral tissue samples (controls) and in tumor material. In 59 of 60 cases, EGFR levels were higher in the tumor than in the corresponding controls. A significant correla-Epidermal growth factor (EGF) is a growth factor polypeptide with a molecular weight of 6,000 daltons, which was described by Cohen' in the mouse submaxillary gland. EGF stimulates the growth of several types of epithelial tissues and diated through its surface receptor (EGFR)* The intracellular component of EGFR is very similar to the V-erb p oncogene product2 In human cancer, the presence of EGFR has been reported in the b r e a~t ,~*~ lung: bladder,6 brain,7 ovaries,' thyroid,' and aerodigestive tract.lO." In these localizations, EGFR has been measured directly, by ligand-binding methods, or indirectly,
2006
Overexpression and mutation of epidermal growth factor receptors (EGFR) have been shown to be important in the prognosis of several cancers, including head and neck cancers. However, our inability to define the activation status of these and other receptors limits our ability to assess the importance of these pathways and to exploit effectively new molecularly targeted treatments directed at their catalytic activities. Here we describe the use of automated, high-throughput fluorescence lifetime imaging microscopy to measure EGFR autophosphorylation status by fluorescence resonance energy transfer (FRET) in head and neck tumors. We have correlated FRET efficiency with the clinical and survival data. The results from head and neck arrays show that high FRET efficiency is correlated with worsening disease-free survival but not with overall survival. This powerful tool could be exploited as a new independent quantitative prognostic factor in clinical decisions and cancer management. (Cancer Res 2006; 66(5): 2834-43)
Clinical Cancer Research, 2005
Background: Several lines of evidence support the epidermal growth factor receptor (EGFR) as a molecular target for therapy in head and neck squamous cell carcinomas (HNSCC). Determination of tumor EGFR levels by conventional immunohistochemistry has not always predicted antitumor efficacy. Quantitative assays may provide more accurate assessment of the level of EGFR receptor in the tumor, which may thus provide more reliable prognostic and predictive information. We studied the prognostic value of quantitative assessment of EGFR in oropharyngeal squamous cell cancers treated with radiotherapy. Experimental Design:We studied EGFR protein expression on a tissue microarray composed of 95 oropharyngeal cancer cases using an in situ molecular-based method of quantitative assessment of protein expression (AQUA) and correlated those with clinical and pathologic data. Automated, quantitative analysis uses cytokeratin to define pixels as cancer (tumor mask) within the array spot and measures intensity of EGFR expression using a Cy5-conjugated antibody within the mask. A continuous index score is generated, which is directly proportional to the number of molecules per unit area, and cases were defined as high expressing if they were above the median expression level. Results: The mean follow-up time for survivors was 44.9 months, and for the entire cohort was 34.8 months. Patients with high tumor EGFR expression levels had a local recurrence rate of 58% compared with 17% for patients with low EGFR tumor expression (P < 0.01). Similarly, patients with high nuclear EGFR expression had a local recurrence rate of 54% compared with 21% for patients with low EGFR nuclear expression (P < 0.05). Additionally, patients with high tumor and nuclear EGFR levels had inferior disease-free survival compared with low expressors (19% versus 43% and 19% versus 45%, respectively. P < 0.05 for each). In multivariate analysis adjusting for well-characterized prognostic variables, high tumor and nuclear EGFR expression levels retained their prognostic significance. Conclusion: The AQUA system provides a continuous measurement of EGFR on paraffinembedded tissue and was able to reveal the association between EGFR expression and outcome expected from the biological role of EGFR. In the future, EGFR AQUA score may be useful in predicting response to EGFR-targeted therapies. Mortality rates of patients with head and neck squamous cell cancer (HNSCC) have not improved substantially over the past 30 years, despite advances in diagnosis and therapy (1).
Research Square (Research Square), 2019
Background: Head and neck Tumour (HNT) are tumour of the paranasal sinuses, the salivary glands and the upper aero¬digestive tract. EGF can stimulate cell proliferation, cell differentiation, cell growth, migration, and inhibit apoptosis. The aim of this study was to investigate the expression of EGFR in head and neck tumour. Method: EGFR expression was analyzed using quantitative real-time PCR (qRT-PCR) and immunohistochemical staining on tissue samples from a consecutive series of 150 head and neck tumour patients who underwent tumor resections between 2014 and 2018. Results: The relationship between EGFR expressions, clinicopathological factors, was investigated. qRT-PCR results showed that the EGFR expression was high in tumor tissue samples than in the normal head and neck tissues. High and low EGFR was compared with ages ≤40,>40 in the head and neck cancer of p-value 0.03. There was a signi cant difference between the histological differentiation of the malignant tumour with p values of 0.001, when well, moderate and poor was compared. There was a signi cant difference (p-value 0.012) between the I-II and III-IV tumour stages when the high level and low expression of EGFR were compared. Conclusion: Our data suggest that EGFR plays an important role in head and neck tumour progression and that its expression will provide baseline data to facilitate identi cation of new molecular targeting therapeutics.
Prognostic Worth of Epidermal Growth Factor Receptor (EGFR) in Patients with Head and Neck Tumors
Journal of Cancer Epidemiology
Introduction. Head and neck tumors (HNT) are tumors that normally occur at the head and neck region of the body. Epidermal growth factor receptor (EGFR) has been found to be highly expressed in breast and other tumors; therefore, there is the need to investigate the level of EGFR expression among patients with head and neck tumors in Ghana. Method. The level of EGFR expression was determined in head and neck tumor and control head and neck tissues with quantitative real-time PCR and immunohistochemistry analysis. Results. The level of EGFR expressions was high in tumor tissues than in the control tissues. There was a significant difference of p value 0.025 among the ages >40 and ≤ 40 when the high and low level of EGFR was compared in the head and neck malignant tumor. The area under the curve for the high expression of EGFR among the malignant head and neck tumors was 0.901 with a specificity of 86.4%. Conclusion. EGFR can serve as a prognostic marker in monitoring patients with...
Oncology letters, 2016
Approximately 90% of all head and neck tumors are squamous cell carcinomas. The overall survival of patients with head and neck squamous cell carcinoma (HNSCC) is low (≤50%). A non-invasive marker of disease progression is sorely required. The present study focused on the plasmatic levels of epidermal growth factor receptor (EGFR) in HNSCC patients (N=92) compared with healthy (N=29) and diabetic [type 2 diabetes mellitus (T2DM); N=26] controls. Enzyme-linked immunosorbent assay using antibodies against the extracellular region of EGFR (L25-S645) was performed. No significant changes were observed between diabetic and healthy controls. However, there were significantly higher EGFR plasma levels in HNSCC patients compared with both control groups (P=0.001 and 0.005, respectively). Receiver operating characteristic curve analysis identified a sensitivity of 76.09%, a specificity of 67.27% and an area under curve of 0.727 for this comparison. No significant association was observed bet...
Analysis of the Epidermal Growth Factor Receptor Gene in Fresh Human Head and Neck Tumors
Cancer Research, 1987
Seventeen fresh uncultured tumors obtained from biopsies of patients with various forms of head and neck cancer and two squamous cell carcinoma cell lines were analyzed for RNA expression and structural alterations of the epidermal growth factor reception gene. We used cDNA probes for the external and the internal domains of the gene. Enhanced inRNA expression was found only in one squamous cell carcinoma cell line, which is known to have high levels of epidermal growth factor receptor. No amplification or structural rearrangement of the epidermal growth factor receptor gene was found.