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, 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.
Reimer
T
T
Department of Obstetrics and Gynecology, University of Rostock, Germany.
Herrnring
C
C
Koczan
D
D
Richter
D
D
Gerber
B
B
Kabelitz
D
D
Friese
K
K
Thiesen
H J
HJ
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
C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D019014:fas Receptor