EGFR and P-GP expression in oropharyngeal mucosa in relation to smoking

About two thirds of head and neck squamous cell carcinoma (HNSCC) cases are attributable to heavy tobacco and alcohol consumption. Tobacco carcinogens cause cellular damage in large areas of the upper aerodigestive tract mucosa and contribute to distinct molecular changes, such as increasing levels of epidermal growth factor receptor (EGFR), during carcinogenesis. P-Glycoprotein (P-GP) is a multidrug-resistance transporter protein capable of extruding not only cytotoxic drugs, but also certain tobacco-related carcinogens. EGFR plays a major role in the transcriptional and functional regulation of P-GP and previous studies in our laboratory showed that stimulation of EGFR protection protected oropharyngeal cells from a carcinogen that is substrate of P-GP. Therefore, we evaluated expression levels of EGFR and P-GP and looked for a possible association with the smoking status of patients.

Tissue cultures of healthy oropharyngeal mucosa were produced from 30 patients undergoing surgery at our Department. Expression levels of EGFR on P-GP were determined by immunohistochemical staining. To evaluate possible influences of EGFR on P-GP expression, we stimulated the receptor using transforming growth factor alpha (TGF-α) for 24, 48 and 72 h.

Current and former smokers had significantly higher EGFR/P-GP levels than never smokers. While EGFR expression was detected in almost all samples, P-GP expression was largely restricted to former and current smokers. TGF-α had no detectable effect on EGFR/P-GP levels.

These results show an association between tobacco use and levels of both proteins. Since both these proteins are involved in drug resistance of head and neck cancer, this study might help to further understand the differences in response to therapy and prognosis of tobacco-related and -unrelated cancer.