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    Tumor-infiltrating FOXP3+ T regulatory cells show strong prognostic significance in colorectal cancer

    Access Status
    Fulltext not available
    Authors
    Salama, P.
    Phillips, M.
    Grieu, F.
    Morris, M.
    Zeps, Nikolajs
    Joseph, D.
    Platell, C.
    Iacopetta, B.
    Date
    2009
    Type
    Journal Article
    
    Metadata
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    Citation
    Salama, P. and Phillips, M. and Grieu, F. and Morris, M. and Zeps, N. and Joseph, D. and Platell, C. et al. 2009. Tumor-infiltrating FOXP3+ T regulatory cells show strong prognostic significance in colorectal cancer. Journal of Clinical Oncology. 27 (2): pp. 186-192.
    Source Title
    Journal of Clinical Oncology
    DOI
    10.1200/JCO.2008.18.7229
    ISSN
    0732-183X
    URI
    http://hdl.handle.net/20.500.11937/40045
    Collection
    • Curtin Research Publications
    Abstract

    Purpose: To determine the prognostic significance of FOXP3+ lymphocyte (Treg) density in colorectal cancer compared with conventional histopathologic features and with CD8+ and CD45RO+ lymphocyte densities. Patients and Methods: Tissue microarrays and immunohistochemistry were used to assess the densities of CD8+, CD45RO+, and FOXP3+ lymphocytes in tumor tissue and normal colonic mucosa from 967 stage II and stage III colorectal cancers. These were evaluated for associations with histopathologic features and patient survival. Results: FOXP3+ Treg density was higher in tumor tissue compared with normal colonic mucosa, whereas CD8+ and CD45RO+ cell densities were lower. FOXP3+ Tregs were not associated with any histopathologic features, with the exception of tumor stage. Multivariate analysis showed that stage, vascular invasion, and FOXP3+ Treg density in normal and tumor tissue were independent prognostic indicators, but not CD8+ and CD45RO+. High FOXP3+ Treg density in normal mucosa was associated with worse prognosis (hazard ratio [HR] = 1.51; 95% CI, 1.07 to 2.13; P = .019). In contrast, a high density of FOXP3 + Tregs in tumor tissue was associated with improved survival (HR = 0.54; 95% CI, 0.38 to 0.77; P = .001). Conclusion: FOXP3+ Treg density in normal and tumor tissue had stronger prognostic significance in colorectal cancer compared with CD8+ and CD45RO+ lymphocytes. The finding of improved survival associated with a high density of tumor-infiltrating FOXP3+ Tregs in colorectal cancer contrasts with several other solid cancer types. The inclusion of FOXP3+ Treg density may help to improve the prognostication of early-stage colorectal cancer. © 2008 by American Society of Clinical Oncology.

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