The "Fas counterattack" is not an active mode of tumor immune evasion in colorectal cancer with high-level microsatellite instability.

Hdl Handle:
http://hdl.handle.net/10147/209253
Title:
The "Fas counterattack" is not an active mode of tumor immune evasion in colorectal cancer with high-level microsatellite instability.
Authors:
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
Affiliation:
Department of Medicine, National University of Ireland Cork, Clinical Science, Building, Cork University Hospital, Wilton, Cork, Ireland. a.houston@ucc.ie
Citation:
Hum Pathol. 2008 Feb;39(2):243-50. Epub 2007 Oct 24.
Journal:
Human pathology
Issue Date:
3-Feb-2012
URI:
http://hdl.handle.net/10147/209253
DOI:
10.1016/j.humpath.2007.06.010
PubMed ID:
17961631
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
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
ISSN:
0046-8177 (Print); 0046-8177 (Linking)

Full metadata record

DC FieldValue Language
dc.contributor.authorHouston, Aileen Men_GB
dc.contributor.authorMichael-Robinson, Julie Men_GB
dc.contributor.authorWalsh, Michael Den_GB
dc.contributor.authorCummings, Margaret Cen_GB
dc.contributor.authorRyan, Aideen Een_GB
dc.contributor.authorLincoln, Douglasen_GB
dc.contributor.authorPandeya, Nirmalaen_GB
dc.contributor.authorJass, Jeremy Ren_GB
dc.contributor.authorRadford-Smith, Graham Len_GB
dc.contributor.authorO'Connell, Joeen_GB
dc.date.accessioned2012-02-03T15:16:19Z-
dc.date.available2012-02-03T15:16:19Z-
dc.date.issued2012-02-03T15:16:19Z-
dc.identifier.citationHum Pathol. 2008 Feb;39(2):243-50. Epub 2007 Oct 24.en_GB
dc.identifier.issn0046-8177 (Print)en_GB
dc.identifier.issn0046-8177 (Linking)en_GB
dc.identifier.pmid17961631en_GB
dc.identifier.doi10.1016/j.humpath.2007.06.010en_GB
dc.identifier.urihttp://hdl.handle.net/10147/209253-
dc.description.abstractMicrosatellite 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.en_GB
dc.language.isoengen_GB
dc.subject.meshAdenocarcinoma/genetics/*metabolism/pathologyen_GB
dc.subject.meshAgeden_GB
dc.subject.meshAntigens, CD3/metabolismen_GB
dc.subject.meshColorectal Neoplasms/genetics/*metabolism/pathologyen_GB
dc.subject.meshFas Ligand Protein/*metabolismen_GB
dc.subject.meshFemaleen_GB
dc.subject.meshFluorescent Antibody Technique, Indirecten_GB
dc.subject.meshHumansen_GB
dc.subject.meshImmune Toleranceen_GB
dc.subject.meshImmunoenzyme Techniquesen_GB
dc.subject.meshLymphocytes, Tumor-Infiltrating/*pathologyen_GB
dc.subject.meshMaleen_GB
dc.subject.mesh*Microsatellite Instabilityen_GB
dc.titleThe "Fas counterattack" is not an active mode of tumor immune evasion in colorectal cancer with high-level microsatellite instability.en_GB
dc.contributor.departmentDepartment of Medicine, National University of Ireland Cork, Clinical Science, Building, Cork University Hospital, Wilton, Cork, Ireland. a.houston@ucc.ieen_GB
dc.identifier.journalHuman pathologyen_GB
dc.description.provinceMunster-

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