The Fas ligand (FasL) and its receptor Fas (APO-1 or CD95) are members, res
pectively, of the tumor necrosis factor family that, upon interaction with
each other, play a key role in the initiation of one apoptotic pathway. Fau
lty regulation of the Fas system has been described in a variety of human t
umors with different histogenetic origin. Here, we describe the expression
and distribution of Fas receptor and ligand pair antigens in surgical sampl
es collected from a cohort of 186 patients bearing breast neoplasms (45 ben
ign and 141 malignant lesions). Immunoperoxidase staining of formalin-fixed
tissues showed that 91.1% of benign lesions expressed Fas, which was prese
nt in only 56.7% of malignant tumors. On the other hand, FasL was found pos
itive in 22.2% of benign neoplasms and up-regulated in in situ as well as i
nvasive carcinomas (53.9%). Moreover, in malignant tumors, the expression o
f receptor and ligand antigens appeared to be inversely related. When these
findings were correlated with pathological parameters of prognostic releva
nce, a significant association was observed between FasL and the presence o
f metastatic lymph nodes and larger tumor size while Fas expression correla
ted to node-negative status and smaller tumor size. patients with Fas posit
ive tumors exhibited longer disease-free survival than those with Fas-negat
ive carcinoma while Fast did not influence patient outcome. These relations
hips indicate that benign and malignant mammary lesions are characterized b
y differential cellular expression of Fas and FasL and suggest that a neopl
astic Fas negative/FasL positive phenotype may be linked to breast cancer p
rogression. (C) 2000 Wiley-Liss, Inc.