title: Impaired CD95 expression predisposes for recurrence in curatively resected colon carcinoma: clinical evidence for immunoselection and CD95L mediated control of minimal residual disease.
abstract: BACKGROUND
  Loss of CD95 expression in tumour cells occurs frequently in colon carcinoma and may be associated with disease progression. On the other hand, neo-expression of CD95L in tumour cells may contribute to immune evasion.
  
  
  OBJECTIVE
  We aimed at further exploring the functional role and prognostic significance of the CD95/CD95L death inducing system in colon carcinomas.
  
  
  METHODS
  CD95 and CD95L expression was examined by immunohistochemistry in 128 R0 resected UICC (International Union against Cancer) stage II/III colon carcinomas and correlated with disease free survival.
  
  
  RESULTS
  CD95 expression in tumour cells was observed in only 30 carcinomas (23.4%) whereas the others had at least a minor subpopulation of CD95 negative cells. Loss of CD95 in tumour cells was related to adverse prognosis in uni- and multivariate analysis (p = 0.046 and p = 0.036, respectively). Tumour infiltrating lymphocytes (TIL) were the major source of CD95L in colon carcinomas. CD95L+TIL were present in 83% of cases whereas CD95L was found in tumour cells in only 12% of cases. Moreover, a high rate of CD95L+TIL correlated with prolonged disease free survival in patients with UICC stage II (p = 0.05) but not in those with stage III.
  
  
  CONCLUSIONS
  Loss of CD95 in tumour cells may be an independent prognostic factor in colon carcinomas. The CD95L counterattack is not a relevant feature in colon carcinoma but CD95L+TIL may contribute to tumour control in the early stages of the disease, exerting a concurrent selection pressure in the direction of CD95 abrogation/resistance.
authors.affiliation: Department of Pathology, University of Ulm, Albert-Einstein-Allee 11, 89081 Ulm, Germany. joern.straeter@medizin.uni-ulm.de
authors.forename: J
authors.initials: J
authors.lastname: Sträter
authors.forename: U
authors.initials: U
authors.lastname: Hinz
authors.forename: C
authors.initials: C
authors.lastname: Hasel
authors.forename: U
authors.initials: U
authors.lastname: Bhanot
authors.forename: G
authors.initials: G
authors.lastname: Mechtersheimer
authors.forename: T
authors.initials: T
authors.lastname: Lehnert
authors.forename: P
authors.initials: P
authors.lastname: Möller
mesh_terms: D000230:Adenocarcinoma / Q000276:immunology* / Q000556:secondary / Q000601:surgery; D000368:Aged; D000951:Antigens, Neoplasm / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism*; D003110:Colonic Neoplasms / Q000276:immunology* / Q000473:pathology / Q000601:surgery; D018572:Disease-Free Survival; D053222:Fas Ligand Protein; D005260:Female; D006801:Humans; D007958:Leukocyte Count; D008024:Ligands; D008207:Lymphatic Metastasis; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008875:Middle Aged; D009367:Neoplasm Staging; D018365:Neoplasm, Residual; D011379:Prognosis; D019014:fas Receptor / Q000378:metabolism*
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008024:Ligands; D008562:Membrane Glycoproteins; D019014:fas Receptor