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Impaired CD95 expression predisposes for recurrence in curatively resected colon carcinoma: clinical evidence for immunoselection and CD95L mediated control of minimal residual disease
  1. J Sträter1,
  2. U Hinz2,
  3. C Hasel1,
  4. U Bhanot1,
  5. G Mechtersheimer3,
  6. T Lehnert2,
  7. P Möller1
  1. 1Department of Pathology, University of Ulm, Ulm, Germany
  2. 2Section of Surgical Oncology/Department of Surgery, University of Heidelberg, Heidelberg, Germany
  3. 3Department of Pathology, University of Heidelberg, Heidelberg, Germany
  1. Correspondence to:
    Dr J Sträter
    Department of Pathology, University of Ulm, Albert-Einstein-Allee 11, 89081 Ulm, Germany; joern.straetermedizin.uni-ulm.de

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.

  • CD95L, CD95 ligand
  • TIL, tumour infiltrating lymphocytes
  • UICC, International Union against Cancer
  • apoptosis
  • CD95
  • colon carcinoma
  • colon cancer
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Footnotes

  • Conflict of interest: None declared

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