Introduction: Retinol acid, which is an essential ligand for the nuclear retinoic acid receptor RAR (α, β, γ) and RXR (α, β, γ) is an important factor for normal cellular differentiation and proliferation. Retinoic metabolism directly influence gene regulation. Disturbances in metabolism of retinoic acid are accused to play a role in the development of esophageal SCC. Induction of cytochrome P450 subclasses, caused by chronic consumption of alcohol and lack of micronutritions in diet, is discussed to alter the cellular bioavailability of retinoic acid. Especially the cytochrome P450 subclasses CYP2C8. CYP2E1, CYP3A4 and CYP3A5 which are in vitro proofed to metabolise retinoic acid into biologic inactive dérivâtes, seem to play an important role in regulation of retinoic acid. The aim of the study was to investigate the protein expression of CYP2C8. CYP2E1. CYP3A4 and CYP3A5 in SCC and normal mucosa of the esophagus.

Material and Methods: From 1 October 1999 to 30 november 2000 19 patients with esophageal SCC underwent preoperative endoscopy. Biopsies were taken from normal esophageal mucosa and tumor. After total protein extraction the specific protein concentration for CYP2C8, CYP2E1, CYP3A4 and CYP3A5 was measured with a semiquantitative immunoblot method (Western blot). For statistical analysis, the Wilcoxon-test for paired samples was used. Statistical significance was considered at p<0.05. 

Results: Protein expression of CYP3A4 was significantly higher in malignant tumor tissue compared to normal mucosa (p<0.05). No significant differences could be found for the protein expression of the other three cytochrome P450 subclasses. 

Conclusion: This study shows that protein expression of CYP3A4 - in contrast to CYP2C8, CYP2E1 and CYP3A5 - was significantly higher in SCC than in healthy tissue of the esophagus. Because of the negative influence of the cytochromes P450 on the retinoic metabolism, which insures normal cell differentation we conclude that changes in expression of CYP3A4 might be one mechanism in the development of SCC of the esophagus.