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

Research output: Contribution to journalArticle

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Abstract

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
Number of pages8
JournalPloS ONE
Volume6
Issue number1
DOIs
Publication statusPublished - 7 Jan 2011

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Macrophages
adenoma
Adenoma
neoplasms
Genes
Colonic Polyps
Adenomatous Polyps
Neoplasms
Cytokine Receptors
T-cells
macrophages
Interleukin-8
Phenotype
Infiltration
Gene expression
Tumors
colorectal neoplasms
Colorectal Neoplasms
phenotype
Carcinogenesis

Keywords

  • adenoma
  • carcinoma
  • colorectal
  • inflammation
  • cytokines

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The inflammatory microenvironment in colorectal neoplasia. / McLean, Mairi H; Murray, Graeme I; Stewart, Keith N; Norrie, Gillian; Mayer, Claus; Hold, Georgina L; Thomson, John; Fyfe, Nicky; Hope, Mairi; Mowat, N Ashley G; Drew, Janice E; El-Omar, Emad M.

In: PloS ONE, Vol. 6, No. 1, e15366, 07.01.2011.

Research output: Contribution to journalArticle

McLean, MH, Murray, GI, Stewart, KN, Norrie, G, Mayer, C, Hold, GL, Thomson, J, Fyfe, N, Hope, M, Mowat, NAG, Drew, JE & El-Omar, EM 2011, 'The inflammatory microenvironment in colorectal neoplasia', PloS ONE, vol. 6, no. 1, e15366. https://doi.org/10.1371/journal.pone.0015366
McLean, Mairi H ; Murray, Graeme I ; Stewart, Keith N ; Norrie, Gillian ; Mayer, Claus ; Hold, Georgina L ; Thomson, John ; Fyfe, Nicky ; Hope, Mairi ; Mowat, N Ashley G ; Drew, Janice E ; El-Omar, Emad M. / The inflammatory microenvironment in colorectal neoplasia. In: PloS ONE. 2011 ; Vol. 6, No. 1.
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AB - 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.

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