Epidermal growth factor receptor expression on oral mucosa dysplastic epithelia and squamous cell carcinomas

Abstract

The expression of the receptor for epidermal growth factor (EGF) has been determined on oral squamous cell carcinomas. Immunoreactive receptor was localized using a monoclonal anti-EGF-receptor antibody which reacts with sequences in the external domain of the receptor. Frozen sections were studied from 40 patients with squamous cell carcinomas. In 16 sections from the patients with the squamous cell carcinomas, normal differentiated oral mucosa was included and in 7 of these the patients had received preoperative radiotherapy. Sections from 6 other patients with squamous cell carcinoma contained dysplastic epithelia. EGF-receptor-positive cells were present in the basal cell layer on normal differentiated oral mucosa. In sections from patients receiving preoperative radiotherapy the EGF-receptor-positive cells were also found in the spinous cells. In dysplastic epithelia nearly all cells stained for the receptor. The distribution and staining intensity of the EGF receptor varied in the oral squamous cell carcinomas, 36 were positive. The staining pattern in the carcinomas obtained from patients receiving preoperative radiotherapy was not altered qualitatively. Nearly all poorly differentiated cells were stained, but when the tumor was moderately to well differentiated a reduction in the extent of staining in certain areas was seen, paralleling the findings observed in the differentiated upper layers of the normal oral mucosa. This was most pronounced for the epithelial pearls, where the EGF-receptor-positive cells were localized to the undifferentiated cells in the periphery. The results of the present investigation confirm the presence of the EGF receptor on undifferentiated cells, with the extent of the staining reaction on oral squamous cell carcinomas varying inversely with cellular differentiation.

Inhibition of epidermal growth factor receptor gene expression and function decreases proliferation of head and neck squamous carcinoma but not normal mucosal epithelial cells

“…We and others have shown that EGFR mRNA and protein is overexpressed in tumors and cell lines obtained from patients with SCCHN (Ozanne et al, 1986;Maxwell et al, 1989;Kawamoto et al, 1991;Christensen et al, 1992;Rubin Grandis and Tweardy, 1993). While EGFR gene ampli®cation has been reported in selected SCCHN cell lines and tumor samples (Yamamoto et al, 1986;Weichselbaum et al, 1989;Ishitoya et al, 1989), most of the evidence suggests that upregulation detected at the mRNA and protein level cannot be accounted for by an increase in gene dosage alone (Eisbruch et al, 1987;Rikimaru et al, 1992).…”

Requirement of Stat3 but not Stat1 activation for epidermal growth factor receptor- mediated cell growth In vitro.

“…Grandis, unpublished observations). Overexpression of TGF-␣ and EGFR (mRNA and protein) has been detected in tumors and cell lines established from patients with head and neck cancer (31,32), and elevated levels of TGF-␣ and/or EGFR have been associated with adverse clinical outcome (33)(34)(35).…”

Immunolocalization of transforming growth factor alpha in normal human tissues

“…Some sections were investigated further by titration of the antibody and in some cases staining was seen at 1:400 and 1:1600 (0.24-0.06 gg/ml) dilutions, e.g., the duodenum and the kidney. The immunoreaction was visualized with alkaline phosphatase/anti-alkaline phosphatase complexes (APAAP) in a five-layer technique (Christensen et al 1992;Cordell et al 1984). After the final incubation with APAAP complexes, the enzyme reaction was visualized with fast red for 1 h (Kem-Entec Copenhagen, Denmark).…”