Clinicopathological significance of indoleamine 2,3-dioxygenase 1 expression in colorectal cancer

被引：120

作者：

Ferdinande, L. ^{[1
]}

Decaestecker, C. ^{[2
]}

Verset, L. ^{[3
]}

Mathieu, A. ^{[3
]}

Lopez, X. Moles ^{[2
,3
]}

Negulescu, A-M ^{[3
]}

Van Maerken, T. ^{[4
]}

Salmon, I. ^{[3
]}

Cuvelier, C. A. ^{[1
]}

Demetter, P. ^{[3
]}

机构：

[1] Univ Ghent, Ghent Univ Hosp, Dept Pathol, B-9000 Ghent, Belgium

[2] Univ Libre Bruxelles, Lab Image Anal & Synth, Brussels, Belgium

[3] Univ Libre Bruxelles, Erasme Univ Hosp, Dept Pathol, Brussels, Belgium

[4] Univ Ghent, Ghent Univ Hosp, Dept Clin Chem Microbiol & Immunol, B-9000 Ghent, Belgium

来源：

BRITISH JOURNAL OF CANCER | 2012年 / 106卷 / 01期

关键词：

indoleamine 2,3-dioxygenase 1; colorectal cancer; immunohistochemistry; tumour invasion front; colon cancer cell lines; BETA-CATENIN; T-CELLS; COLON-CANCER; TRYPTOPHAN DEGRADATION; INTERFERON-GAMMA; IMMUNE-RESPONSE; MICE; QUANTIFICATION; INFLAMMATION; SUPPRESSION;

D O I：

10.1038/bjc.2011.513

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

BACKGROUND: Indoleamine 2,3-dioxygenase 1 (IDO1) is a tryptophan-catabolising enzyme that induces immune tolerance by modulating T-cell responses. Carcinomas may create an immunosuppressive state via IDO1 expression. Here we examined a possible contribution of IDO1 on this phenomenon and investigated whether IDO1 has prognostic value in colorectal cancer (CRC). METHODS: IDO1 expression was investigated by quantitative PCR and western blotting in three colon cancer cell lines, in basal state and after interferon (IFN)-gamma stimulation. Semi-quantitative immunohistochemistry was used to evaluate IDO1 expression in 265 pT1-4N0-2Mx-staged CRCs. Results were related to clinical variables and correlated with amounts of CD3(+) and CD8(+) T lymphocytes, which were quantitatively evaluated using image analysis. RESULTS: In vitro expression of IDO1 depended on IFN-gamma stimulation. Higher IDO1 expression at the tumour invasion front was an independent adverse prognostic factor in pT1-4N1Mx-staged CRC. It was associated with overall survival (P = 0.001) and with metachronous metastases (P = 0.018). IDO1 expression was not associated with the presence of CD3(+) or CD8(+) T lymphocytes. CONCLUSION: Higher IDO1 expression at the tumour invasion front is involved in CRC progression and correlates with impaired clinical outcome, suggesting that IDO1 is an independent prognostic indicator for CRC. British Journal of Cancer (2012) 106, 141-147. doi:10.1038/bjc.2011.513 www.bjcancer.com Published online 22 November 2011 (C) 2012 Cancer Research UK

引用

页码：141 / 147

页数：7

共 34 条

[1]

MUC1 and nuclear β-catenin are coexpressed at the invasion front of colorectal carcinomas and are both correlated with tumor prognosis [J].