title: Clinicopathological significance of indoleamine 2,3-dioxygenase 1 expression in colorectal cancer.
abstract: 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)-γ 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-γ 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.
  
  
  CONCLUSIONS
  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.
authors: Department of Pathology, Ghent University Hospital, Universiteit Gent, Block A, 5th floor, De Pintelaan 185, B-9000 Ghent, Belgium. Liesbeth.Ferdinande@UGent.be
authors: L
authors: L
authors: Ferdinande
authors: C
authors: C
authors: Decaestecker
authors: L
authors: L
authors: Verset
authors: A
authors: A
authors: Mathieu
authors: X
authors: X
authors: Moles Lopez
authors: A-M
authors: AM
authors: Negulescu
authors: T
authors: T
authors: Van Maerken
authors: I
authors: I
authors: Salmon
authors: C A
authors: CA
authors: Cuvelier
authors: P
authors: P
authors: Demetter
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015153:Blotting, Western; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase