title: FasL:Fas ratio--a prognostic factor in breast carcinomas.
abstract: Programmed cell death (apoptosis) is primarily mediated by Fas ligand (FasL; CD95L) and the Fas receptor (Fas; CD95). In this study, FasL was detected by immunohistochemical analysis in 85% of breast carcinomas and 14% of fibroadenomas randomly chosen, indicating that high expression of FasL might play a role in tumor pathology. FasL and Fas levels as well as FasL:Fas ratios were further ascertained in 215 human breast tumors, including 199 invasive ductal carcinomas, by real-time quantitative reverse transcription-PCR and compared with expression levels and ratios found in 25 normal human tissues, in 37 fibroadenomas, and in 5 normal breast tissues. Among breast carcinomas, high FasL mRNA expression seems to be positively correlated with histological grading (n = 212; P<0.0001). A ratio of FasL:Fas mRNA transcripts >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 strategies.
authors.affiliation: Department of Obstetrics and Gynecology, University of Rostock, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Reimer
authors.forename: C
authors.initials: C
authors.lastname: Herrnring
authors.forename: D
authors.initials: D
authors.lastname: Koczan
authors.forename: D
authors.initials: D
authors.lastname: Richter
authors.forename: B
authors.initials: B
authors.lastname: Gerber
authors.forename: D
authors.initials: D
authors.lastname: Kabelitz
authors.forename: K
authors.initials: K
authors.lastname: Friese
authors.forename: H J
authors.initials: HJ
authors.lastname: Thiesen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000737:chemistry / Q000473:pathology*; D053222:Fas Ligand Protein; D005260:Female; D018226:Fibroadenoma / Q000737:chemistry / Q000473:pathology; D018628:Gene Dosage; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis* / Q000235:genetics; D008875:Middle Aged; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019014:fas Receptor / Q000032:analysis* / Q000235:genetics
chemical_list: C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D019014:fas Receptor