Die Down-Regulation von FAS (APO-l/CD95) begiinstigt die Metastasierung beim Osophaguskarzinom Down regulation of Fas (AP01ICD9S) seems to promote metastasis in esophageal cancer

The cell surface receptor Fas (APO-1/CD95) mediates apoptosis via interaction with its li­ gand (FasL). Fas is normally expressed in a variety of adult tissues including epithelial tis­ sue, whereas FasL expression is predominantly restricted to cells of the immune system or immunoprivileged tissues. In tumors, modulation of Fas and FasL expression is fre­ quent. There is evidence that tumors may escape from immune surveillance via downreg­ ulation of Fas or expression of soluble FasL. Furthermore, upregulation of FasL on cells may induce apoptosis in infiltrating cytotoxic T-cells (counter attack model). So far, little is known about the role of Fas and FasL expression in the progression of esophageal carcinoma. We therefore analyzed cytostat sections of 70 esophageal carcino­ mas with tumor-free resection margins (Ro) for Fas and FasL expression immunohisto­ chemically with the ABC technique using the monoclonal anti-Fas antibody DX2 (Pharm­ ingen) and the polyclonal anti-FasL antibody Q20 (Santa Cruz Biotech.). Stained sections were evaluated semiquantitatively. Staining intensity was also taken into account. In total, 49 of 70 (70%) tumors showed downregulation of Fas, whereas upregulation of FasL was observed in 55 of 70 (79%) cases. Correlation of Fas data with nodal micro dissemination status revealed that patients with Fas downregulation of their primary tumors showed isolated cells in apparently tumor free lymph nodes more frequently than pa­ tients with normal Fas expression (60% vs. 23%; P = 0.01). Moreover, 46% of patients with Fas downregulation developed metastatic relapse within a mean time of 33 month com­ pared to 8% of patients with normal Fas expression within a mean time of 68 months (p = 0.026). In conclusion, modulations of Fas and FasL expression are frequent events in esophageal carcinoma. Furthermore, downregulation of Fas seems to playa role in cell dissemination and/or establishment of metastases in secondary organs via mediation of apoptotic resistance.