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Prognostic relevance of altered Fas (CD95)‐system in human breast cancer
Author(s) -
Mottolese Marcella,
Buglioni Simonetta,
Bracalenti Carla,
Cardarelli Marco Andrea,
Ciabocco Luciana,
Giannarelli Diana,
Botti Claudio,
Natali Pier Giorgio,
Concetti Antonio,
Venanzi Franco Maria
Publication year - 2000
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(20000320)89:2<127::aid-ijc5>3.0.co;2-4
Subject(s) - fas ligand , fas receptor , pathology , breast cancer , lymph node , antigen , cancer , breast carcinoma , biology , mammary gland , apoptosis , medicine , cancer research , immunology , programmed cell death , biochemistry
The Fas ligand (FasL) and its receptor Fas (APO‐1 or CD95) are members, respectively, of the tumor necrosis factor family that, upon interaction with each other, play a key role in the initiation of one apoptotic pathway. Faulty regulation of the Fas system has been described in a variety of human tumors with different histogenetic origin. Here, we describe the expression and distribution of Fas receptor and ligand pair antigens in surgical samples collected from a cohort of 186 patients bearing breast neoplasms (45 benign and 141 malignant lesions). Immunoperoxidase staining of formalin‐fixed tissues showed that 91.1% of benign lesions expressed Fas, which was present in only 56.7% of malignant tumors. On the other hand, FasL was found positive in 22.2% of benign neoplasms and up‐regulated in in situ as well as invasive carcinomas (53.9%). Moreover, in malignant tumors, the expression of receptor and ligand antigens appeared to be inversely related. When these findings were correlated with pathological parameters of prognostic relevance, a significant association was observed between FasL and the presence of metastatic lymph nodes and larger tumor size while Fas expression correlated to node‐negative status and smaller tumor size. Patients with Fas positive tumors exhibited longer disease‐free survival than those with Fas‐negative carcinoma while FasL did not influence patient outcome. These relationships indicate that benign and malignant mammary lesions are characterized by differential cellular expression of Fas and FasL and suggest that a neoplastic Fas negative/FasL positive phenotype may be linked to breast cancer progression. Int. J. Cancer (Pred. Oncol.) 89:127–132, 2000. © 2000 Wiley‐Liss, Inc.