Characterization, quantification, and potential clinical value of the epidermal growth factor receptor in head and neck squamous cell carcinomas

Abstract

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 +/- 0.108 nM (0.095-0.347 nM). EGF-binding characteristics (Kd) 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 correlation 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 fmol/mg protein, which separated all controls from tumors, EGFR-positive tumors (greater than 100 fmol/mg protein) had a greater probability of complete response to chemotherapy than EGFR-negative 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.

Characterization of newly established oral cancer cell lines derived from six squamous cell carcinoma and two mucoepidermoid carcinoma cells

“…Several studies have demonstrated the over expression of EGFR in primary oral cancers and OSC cell lines (Frank et al, 1991;Satini et al, 1991;Shirasuna et al, 1991). Our results showed the over expression of EGFR in newly established YD cell lines.…”

Sequence-dependent effects of ZD1839 (‘Iressa’) in combination with cytotoxic treatment in human head and neck cancer

“…Over the past decade, comprehensive data have been accumulated that strongly support a role for EGFR and its ligands in tumour development and growth. This is particularly true for squamous cell carcinoma of the head and neck, where EGFR is considered to be one of the major prognostic factors (Santini et al, 1991;Dassonville et al, 1993;Salomon et al, 1995;Grandis et al, 1996Grandis et al, , 1998Maurizi et al, 1996). As a result, EGFR has become an attractive target for novel anticancer therapies, particularly in HNC.…”

“…High levels of EGFR expression have been correlated with poor prognosis (Santini et al, 1991;Dassonville et al, 1993). EGFR signalling has been found to control not only cell growth, but also angiogenesis and DNA repair (Wheeler et al, 1999;Schlessinger, 2000), and has recently been assessed as an innovative target in cancer therapy and particularly in HNC.…”

Response of Nasopharyngeal Carcinoma Cells to Epstein-Barr Virus Infection In Vitro

“…(In our unpublished data we have also included other cytokines, such as IL-4, IL-8, and 1155 IL-10, for the studies, and all of them showed no specific change). The fact that the expression of EGFR mRNA increased in the 2 to 3 weeks after EBV infection and then gradually decreased to the original level by 4 weeks after infection indicates that EBV infection activates the host cellular EGFR expression, which may result in an increase in the rate of cellular proliferation through a paracrine or autocrine pathway (Boonstra et al, 1995;Santini et al, 1991;Zheng et al, 1994).…”