Impaired CD95 expression predisposes for recurrence in curatively resected colon carcinoma: clinical evidence for immunoselection and CD95L mediated control of minimal residual disease.
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.
Sträter
J
J
Department of Pathology, University of Ulm, Albert-Einstein-Allee 11, 89081 Ulm, Germany. joern.straeter@medizin.uni-ulm.de
Hinz
U
U
Hasel
C
C
Bhanot
U
U
Mechtersheimer
G
G
Lehnert
T
T
Möller
P
P
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*
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008024:Ligands; D008562:Membrane Glycoproteins; D019014:fas Receptor