The inflammatory microenvironment in colorectal Neoplasia

Mairi H. McLean, Graeme I. Murray, Keith N. Stewart, Gillian Norrie, Claus Mayer, Georgina L. Hold, John Thomson, Nicky Fyfe, Mairi Hope, N. Ashley G. Mowat, Janice E. Drew, Emad M. El-Omar (Lead / Corresponding author)

    Research output: Contribution to journalArticlepeer-review

    152 Citations (Scopus)
    74 Downloads (Pure)

    Abstract

    Colorectal cancer (CRC) is a major cause of mortality and morbidity worldwide. Inflammatory activity within the stroma of invasive colorectal tumours is known to be a key predictor of disease activity with type, density and location of immune cells impacting on patient prognosis. To date, there has been no report of inflammatory phenotype within pre-malignant human colonic adenomas. Assessing the stromal microenvironment and particularly, inflammatory activity within colorectal neoplastic lesions is central to understanding early colorectal carcinogenesis. Inflammatory cell infiltrate was assessed by immunohistochemistry in paired colonic adenoma and adjacent normal colonic mucosa samples, and adenomas exhibiting increasing degrees of epithelial cell dysplasia. Macrophage phenotype was assessed using double stain immunohistochemistry incorporating expression of an intracellular enzyme of function. A targeted array of inflammatory cytokine and receptor genes, validated by RT-PCR, was used to assess inflammatory gene expression. Inflammatory cell infiltrates are a key feature of sporadic adenomatous colonic polyps with increased macrophage, neutrophil and T cell (specifically helper and activated subsets) infiltration in adenomatous colonic polyps, that increases in association with characteristics of high malignant potential, namely, increasing degree of cell dysplasia and adenoma size. Macrophages within adenomas express iNOS, suggestive of a pro-inflammatory phenotype. Several inflammatory cytokine genes (CXCL1, CXCL2, CXCL3, CCL20, IL8, CCL23, CCL19, CCL21, CCL5) are dysregulated in adenomas. This study has provided evidence of increased inflammation within pre-malignant colonic adenomas. This may allow potential mechanistic pathways in the initiation and promotion of early colorectal carcinogenesis to be identified.

    Original languageEnglish
    Article numbere15366
    Pages (from-to)1-8
    Number of pages8
    JournalPLoS ONE
    Volume6
    Issue number1
    DOIs
    Publication statusPublished - 7 Jan 2011

    ASJC Scopus subject areas

    • General Biochemistry,Genetics and Molecular Biology
    • General Agricultural and Biological Sciences
    • General

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