Prognostic relevance of altered Fas (CD95)-system in human breast cancer

Citation
M. Mottolese et al., Prognostic relevance of altered Fas (CD95)-system in human breast cancer, INT J CANC, 89(2), 2000, pp. 127-132
Citations number
36
Categorie Soggetti
Onconogenesis & Cancer Research
Journal title
INTERNATIONAL JOURNAL OF CANCER
ISSN journal
00207136 → ACNP
Volume
89
Issue
2
Year of publication
2000
Pages
127 - 132
Database
ISI
SICI code
0020-7136(20000320)89:2<127:PROAF(>2.0.ZU;2-E
Abstract
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.