FasL : Fas ratio - A prognostic factor in breast carcinomas

Programmed cell death (apoptosis) is primarily mediated by Fas ligand (FasL ; CD95L) and the Fas receptor (Fas; CD95). In this study, Fasb, was detecte d by immunohistochemical analysis in 85% of breast carcinomas and 14% of fi broadenomas randomly chosen, indicating that high expression of Fast might play a role in turner pathology. Fast and Fas levels as well as FasL:Fas ra tios were further ascertained in 215 human breast tumors, including 199 inv asive ductal carcinomas, by real-time quantitative reverse transcription-PC R and compared with expression levels and ratios found in 25 normal human t issues, in 37 fibroadenomas, and in 5 normal breast tissues. Among breast c arcinomas, high Fast mRNA expression seems to be positively correlated with histological grading (n = 212; P < 0.0001). A ratio of FasL:Fas mRNA trans cripts > 1 is found to be significantly associated with decreased patient's disease-free survival (n = 211; P < 0.03) and increased mortality (n = 211 ; P = 0.19), A FasL:Fas ratio > 1 is related to tumor progression scored by histological grading (n = 212; P < 0.02). The selection process leading to highly aggressive breast tumor variants might be enhanced by FasL-mediated tumor fratricide, eventually a possible target for novel therapeutic strat egies.