Fas ligand and tumour counter-attack in colorectal cancer stratified according to microsatellite instability status

Michael-Robinson, Julie M., Pandeya, Nirmala, Cummings, Margaret C., Walsh, Michael D., Young, Joanne P., Leggett, Barbara A., Purdie, David M., Jass, Jeremy R. and Radford-Smith, Graham L. (2003) Fas ligand and tumour counter-attack in colorectal cancer stratified according to microsatellite instability status. Journal of Pathology, 201 1: 46-54. doi:10.1002/path.1406

Author Michael-Robinson, Julie M.
Pandeya, Nirmala
Cummings, Margaret C.
Walsh, Michael D.
Young, Joanne P.
Leggett, Barbara A.
Purdie, David M.
Jass, Jeremy R.
Radford-Smith, Graham L.
Title Fas ligand and tumour counter-attack in colorectal cancer stratified according to microsatellite instability status
Journal name Journal of Pathology   Check publisher's open access policy
ISSN 0022-3417
Publication date 2003-09
Sub-type Article (original research)
DOI 10.1002/path.1406
Volume 201
Issue 1
Start page 46
End page 54
Total pages 9
Editor C. S. Herrington
Place of publication Chichester, U.K.
Publisher John Wiley & Sons
Collection year 2003
Language eng
Subject C1
321020 Pathology
730108 Cancer and related disorders
110316 Pathology (excl. Oral Pathology)
1112 Oncology and Carcinogenesis
Abstract Expression of membrane-bound Fas ligand (FasL) by colorectal cancer cells may allow the development of an immune-privileged site by eliminating incoming tumour-infiltrating lymphocytes (TILs) in a Fas-mediated counter-attack. Sporadic colorectal cancer can be subdivided into three groups based on the level of DNA microsatellite instability (NISI). High-level NISI (NISI-High) is characterized by the presence of TILs and a favourable prognosis, while microsatellite-stable (MSS) cancers are TIL-deficient and low-level MSI (MSI-Low) is associated with an intermediate TIL density. The purpose of this study was to establish the relationship between MSI status and FasL expression in primary colorectal adenocarcinoma. Using immunohistochemistry and a selected series of 101 cancers previously classified as 31 MSI-High, 30 NISI-Low, and 40 MISS, the present study sought to confirm the hypothesis that increased TIL density in MSI-High cancers is associated with low or absent membrane-bound FasL expression, while increased FasL in MSS cancers allows the killing of host TILs. TUNEL/CD3 double staining was also used to determine whether MSS cancers contain higher numbers of apoptotic TILs in vivo than MSI-High or MSI-Low cancers. Contrary to the initial hypothesis, it was found that MSI-High cancers were associated with higher FasL expression (p = 0.04) and a stronger intensity of FasL staining (p = 0.007). In addition, mucinous carcinomas were independently characterized by increased FasL expression (p = 0.03) and staining intensity (p = 0.0005). Higher FasL expression and staining intensity did not correlate with reduced TIL density or increased numbers of apoptotic TILs. However, consistent with the hypothesis that curtailment of the host anti-tumour immune response contributes to the poor prognosis in MSS cancers, it was found that apoptotic TILs were most abundant in MSS carcinomas and metastatic Dukes' stage C or D tumours (p = 0.004; p = 0.046 respectively). This study therefore suggests that MSS colorectal cancers are killing incoming TILs in an effective tumour counter-attack, but apparently not via membrane-bound FasL. Copyright (C) 2003 John Wiley Sons, Ltd.
Keyword Pathology
Microsatellite Instability
Fas Ligand
Immune Privilege
Tumour-infiltrating Lymphocyte
Dna-replication Errors
Cell-surface Antigen
Infiltrating Lymphocytes
Immune Evasion
Receptor Superfamily
Induced Apoptosis
Liver Metastases
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
2004 Higher Education Research Data Collection
School of Medicine Publications
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Citation counts: TR Web of Science Citation Count  Cited 9 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 13 times in Scopus Article | Citations
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Created: Tue, 14 Aug 2007, 19:19:09 EST