CD Markers
CD95

Author: Nat Pernick, M.D. (see Authors page)

Revised: 16 December 2015, last major update September 2013

Copyright: (c) 2003-2015, PathologyOutlines.com, Inc.

PubMed Search: CD95[title]
Definition / General
  • Also called Fas, Apo-1, TNF receptor superfamily member 6, TNFRSF6
  • Cell surface membrane receptor that activates apoptotic pathways when bound by Fas ligand (FasL, CD178)
  • Extrinsic pathway: activation leads to assembly of a death inducing signaling complex (DISC) consisting of CD95, the Fas-associated death domain (FADD) adapter protein, the initiator caspase-8 (previously called FLICE or MACH) and cellular FLICE inhibitory protein (cFLIP), a regulatory protein that can block or promote autoproteolytic conversion of pro-caspase-8 to caspase-8 within the DISC; caspase 8 activates a cascade of caspases that ultimately activates caspase 3, which mediates apoptosis
  • Intrinsic pathway: involves release of cytochrome c from mitochondria, which complexes with apoptosis inducing factor 1, procaspase 9 and ATP, leading to caspase 9 activation, which activates caspase 3
  • Fas-FasL system mediates extra-thymic self-tolerance (FasL+ cells induce apoptosis in infiltrating Fas+ lymphocytes in testis, cornea), T cell mediated cytotoxicity, apoptosis during development, halting of immune response
  • Defects in Fas-Fas ligand pathway (usually Fas but occasionally FasL germline mutations) cause autoimmune lymphoproliferative syndrome, a rare childhood disorder associated with B cell lymphomas, classic Hodgkin’s lymphoma and nodular lymphocyte predominant Hodgkin’s lymphoma (Leuk Lymphoma 2004;45:423)
  • CD95 downregulation may reduce CD4+ T cells in HIV (Arch Pathol Lab Med 2002;126:28)
  • May be involved in clearance of benign ovarian epithelial inclusion cysts; derangement in pathway may cause ovarian surface epithelial carcinomas (Hum Pathol 2005;36:971)
  • Polymorphisms in Fas or FasL: associated with increased risk of autoimmune hepatitis (Am J Gastroenterol 2005;100:1322), increased risk of type II diabetes (Genes Immun 2006;7:316); Fas -670 AG genotype is associated with increased risk of preterm premature rupture of membranes (Am J Obstet Gynecol 2005;193:1132); Fas -670 AA genotype is associated with reduced liver graft survival (Tissue Antigens 2006;67:117); FAS -1377AA genotype is associated with increased risk of lung cancer (J Med Genet 2005;42:479)
Prognostic Factors
Diagrams / Tables

Cytotoxic T lymphocyte pathway

Uses by Pathologists
  • Prognostic factors (above)
Micro Images

Images hosted on other servers:

Normal kidney (FasL-left, Fas-right)

Lymph node of HIV patient


Malignancies:

Extrahepatic bile duct carcinoma (figures C-H)

Renal cell carcinoma
(FasL-left, Fas-right)

Positive Staining - Normal
  • Activated B cells, activated T cells (initially extra but nonfunctional Fas), resting T cells (low levels), numerous epithelium and connective tissue
Positive Staining - Disease
Negative Staining
  • Invasive ovarian carcinoma
Additional References