Expression of TRAIL and TRAIL receptors in colon carcinoma: TRAIL-R1 is an independent prognostic parameter.
OBJECTIVE
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) selectively induces apoptosis in cancer cells and may be involved in protection from metastases. TRAIL receptor (TRAIL-R) 1 and TRAIL-R2, but not TRAIL-R3 and TRAIL-R4, mediate apoptosis. We examined the expression of TRAIL and its receptors in normal and neoplastic colon epithelium, and studied its correlation with prognosis in colon cancer.


METHODS
Immunohistochemistry was performed on normal colon mucosa (n = 10), colon adenomas (n = 20), and R0-resected Unio Internationale Contra Cancrum stage II/III colon carcinomas (n = 129). Disease-free survival was examined by Kaplan-Meier estimates and the log-rank test. Prognostic factors were determined by multivariate Cox-analysis.


RESULTS
In normal colon mucosa, TRAIL and TRAIL-R2 were expressed mostly in the surface epithelium, whereas TRAIL-R1 and TRAIL-R4 were detected all along the crypt axis. In adenomas, this expression pattern was mostly retained, although some adenomas also neoexpressed TRAIL-R3. In carcinomas, the expression of TRAIL and TRAIL receptors was much more variable. TRAIL, TRAIL-R2, TRAIL-R3, and TRAIL-R4 expression did not correlate statistically with disease-free survival (multivariate analysis: P = 0.54, P = 0.67, P = 0.45, and P = 0.69, respectively), but TRAIL-R1 expression was significantly associated with disease-free survival in colon cancer (multivariate analysis: P = 0.003).


CONCLUSIONS
TRAIL-R1 is an independent prognostic factor in R0-resected Unio Internationale Contra Cancrum stage II/III colon cancer.
Sträter
Jörn
J
Department of Pathology, University of Ulm, 89081 Ulm , Germany.
Hinz
Ulf
U
Walczak
Henning
H
Mechtersheimer
Gunhild
G
Koretz
Karin
K
Herfarth
Christian
C
Möller
Peter
P
Lehnert
Thomas
T
D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology; D002288:Adenocarcinoma, Mucinous / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D017209:Apoptosis; D016022:Case-Control Studies; D002454:Cell Differentiation; D003106:Colon / Q000378:metabolism*; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology; D018450:Disease Progression; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D058851:GPI-Linked Proteins; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D053320:Receptors, Tumor Necrosis Factor, Member 10c; D015996:Survival Rate; D053319:Tumor Necrosis Factor Decoy Receptors
D058851:GPI-Linked Proteins; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor; D053320:Receptors, Tumor Necrosis Factor, Member 10c; C105190:TNFRSF10A protein, human; C505639:TNFRSF10B protein, human; C108661:TNFRSF10C protein, human; D053319:Tumor Necrosis Factor Decoy Receptors