Peer-Reviewed Journal Details
Mandatory Fields
Houston, AM,Michael-Robinson, JM,Walsh, MD,Cummings, MC,Ryan, AE,Lincoln, D,Pandeya, N,Jass, JR,Radford-Smith, GL,O'Connell, J
2008
February
Human Pathology
The "Fas counterattack" is not an active mode of tumor immune evasion in colorectal cancer with high-level microsatellite instability
Published
()
Optional Fields
immunohistochemistry Fas ligand microsatellite instability tumor-infiltrating lymphocyte DNA-REPLICATION ERRORS INFILTRATING LYMPHOCYTES COLON-CANCER LIGAND EXPRESSION GASTRIC-CANCER T-LYMPHOCYTES CD95 LIGAND IN-VIVO APOPTOSIS CARCINOMA
39
243
250
Microsatellite instability (MSI) is an alternative pathway of colorectal carcinogenesis. It is found in 10% to 15% of sporadic colorectal neoplasms and is characterized by failure of the DNA mismatch-repair system. High-level MSI (MSI-H) is associated with tumor-infiltrating lymphocytes (TILs) and a favorable prognosis. Expression of Fas ligand (FasL/CD95L) by cancer cells may mediate tumor immune privilege by inducing apoptosis of antitumor immune cells. The aim of this study was to investigate the relationship between FasL expression and MSI status in primary colon tumors. Using immunohistochemistry, we detected FasL expression in 91 colorectal carcinoma specimens, previously classified according to the level of MSI as MSI-H (n = 26), MSI-low (MSI-L) (n = 29), and microsatellite stable (n = 36). Tumor-infiltrating lymphocyte density was quantified by immunohistochemical staining for CD3. MSI-H tumors were significantly associated with reduced frequency (P = .04) and intensity (P = .066) of FasL expression relative to non-MSI-H (ie, microsatellite stable and MSI-L) tumors. Higher FasL staining intensity correlated with reduced TIL density (P = .059). Together, these findings suggest that the abundance of TILs found in MSI-H tumors may be due to the failure of these tumor cells to up-regulate FasL and may explain, in part, the improved prognosis associated with these tumors. (C) 2008 Elsevier Inc. All rights reserved.
DOI 10.1016/j.humpath.2007.06.010
Grant Details
Publication Themes