Impaired CD95 expression predisposes for recurrence in curatively resected colon carcinoma: clinical evidence for immunoselection and CD95L mediated control of minimal residual disease

Gut. 2005 May;54(5):661-5. doi: 10.1136/gut.2004.052696.

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.

Aims: We aimed at further exploring the functional role and prognostic significance of the CD95/CD95L death inducing system in colon carcinomas.

Patients and 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / immunology*
  • Adenocarcinoma / secondary
  • Adenocarcinoma / surgery
  • Aged
  • Antigens, Neoplasm / metabolism
  • Biomarkers, Tumor / metabolism*
  • Colonic Neoplasms / immunology*
  • Colonic Neoplasms / pathology
  • Colonic Neoplasms / surgery
  • Disease-Free Survival
  • Fas Ligand Protein
  • Female
  • Humans
  • Leukocyte Count
  • Ligands
  • Lymphatic Metastasis
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Male
  • Membrane Glycoproteins / metabolism*
  • Middle Aged
  • Neoplasm Staging
  • Neoplasm, Residual
  • Prognosis
  • fas Receptor / metabolism*

Substances

  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • FASLG protein, human
  • Fas Ligand Protein
  • Ligands
  • Membrane Glycoproteins
  • fas Receptor