Prognostic significance of TRAIL-R1 and TRAIL-R3 expression in metastatic colorectal carcinomas.
Drug resistance is believed to cause treatment failure in patients with metastatic colorectal carcinoma (CRC). Resistance to chemotherapy can involve different processes, including apoptosis, whose extrinsic pathway is regulated by expression of death-inducing TRAIL-R1 and -R2 and inhibitory TRAIL-R3 and -R4 cell surface receptors. Therefore, we investigated whether variations in their expression could influence the response to 5-Fluorouracil (5-FU) in metastatic CRC. We analysed TRAIL-R 1, -2, -3 and -4 expression by immuno-histochemistry in CRC, using tissue micro arrays, and found that concomitant low/medium TRAIL-R1 and high TRAIL-R3 expression in primary CRC is significantly associated with a poor response to 5-FU-based first-line chemotherapy and with shorter progression-free survival. Specifically, the median progression-free survival was 3.1 months (poor prognostic group) versus 10.1 in the good prognostic group. Thus, the combination of TRAIL-R1 and TRAIL-R3 expression might represent a predictive and prognostic factor of the response to 5-FU-based first-line chemotherapy in patients with metastatic CRC.
Granci
Virginie
V
Institut de Recherche en Cancérologie de Montpellier (IRCM), INSERM, U896, Université Montpellier1, CRLC Val d'Aurelle Paul Lamarque, 208 rue des Apothicaires, F-34298 Montpellier Cedex 5, France.
Bibeau
Frédéric
F
Kramar
Andrew
A
Boissière-Michot
Florence
F
Thézénas
Simon
S
Thirion
Agnès
A
Gongora
Céline
C
Martineau
Pierre
P
Del Rio
Maguy
M
Ychou
Marc
M