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The "Fas counterattack" is not an active mode of tumor immune evasion in colorectal cancer with high-level microsatellite instability.
Houston, Aileen M Michael-Robinson, Julie M Walsh, Michael D Cummings, Margaret C Ryan, Aideen E Lincoln, Douglas Pandeya, Nirmala Jass, Jeremy R Radford-Smith, Graham L O'Connell, Joe
Houston, Aileen M
Michael-Robinson, Julie M
Walsh, Michael D
Cummings, Margaret C
Ryan, Aideen E
Lincoln, Douglas
Pandeya, Nirmala
Jass, Jeremy R
Radford-Smith, Graham L
O'Connell, Joe
Advisors
Editors
Other Contributors
Date
2012-02-03T15:16:19Z
Date Submitted
Keywords
Other Subjects
Subject Mesh
Adenocarcinoma/genetics/*metabolism/pathology
Aged
Antigens, CD3/metabolism
Colorectal Neoplasms/genetics/*metabolism/pathology
Fas Ligand Protein/*metabolism
Female
Fluorescent Antibody Technique, Indirect
Humans
Immune Tolerance
Immunoenzyme Techniques
Lymphocytes, Tumor-Infiltrating/*pathology
Male
*Microsatellite Instability
Aged
Antigens, CD3/metabolism
Colorectal Neoplasms/genetics/*metabolism/pathology
Fas Ligand Protein/*metabolism
Female
Fluorescent Antibody Technique, Indirect
Humans
Immune Tolerance
Immunoenzyme Techniques
Lymphocytes, Tumor-Infiltrating/*pathology
Male
*Microsatellite Instability
Planned Date
Start Date
Collaborators
Principal Investigators
Alternative Titles
Publisher
Abstract
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.
Language
eng
ISSN
0046-8177 (Print)
0046-8177 (Linking)
0046-8177 (Linking)
eISSN
ISBN
DOI
10.1016/j.humpath.2007.06.010
PMID
17961631