BACKGROUND: There is increasing evidence that the Fas/Fas ligand (FasL) system is involved in tumor-mediated immune suppression. The purpose of this study was to investigate the effect of Fas (CD95) as well as FasL (CD95L) expression in primary malignant melanoma and melanoma metastases on overall survival (OS). PATIENTS AND METHODS: 19 patients with metastatic malignant melanoma who were treated with different dacarbazine (DTIC)-based chemotherapy regimens were included in this study. From each patient, primary melanoma biopsies and biopsies from metastases were histologically evaluated. Immunohistology was performed with antibodies to Fas/CD95 and FasL/CD95L. Differences in OS were plotted using the Kaplan-Meier method and compared by the log rank test. RESULTS: Fas/CD95 and FasL/CD95L expression was detected in 73.7 and 63.2% of primary melanomas, respectively. In metastases, expression of both Fas/CD95 (63.2%) and FasL/CD95L (47.4%) was markedly decreased. Presence of FasL/ CD95L expression in primary melanoma resulted in significantly (p = 0.024) prolonged OS compared with FasL/CD95L-negative high-risk primary melanomas. In contrast, loss of FasL/CD95L expression in melanoma metastases resected before chemotherapy was associated with significantly prolonged median survival (p = 0.0139). CONCLUSION: Presence of FasL/CD95L expression in primary malignant melanoma and the loss of FasL/ CD95L expression in metastases seem to be positive prognostic factors.
