title: Expression and prognostic impact of indoleamine 2,3-dioxygenase in oral squamous cell carcinomas.
abstract: Indoleamine 2,3 dioxygenase (IDO) is a negative immune regulator and was found to be a prognostic marker in several tumor entities. In this study, we analysed IDO expression in oral squamous cell carcinoma (OSCC) regarding patient's prognosis. Additionally, expression of IDO like-1 gene (INDOL-1) was analysed. Tumor tissue from 88 patients with OSCC was analysed by immunohistochemistry for IDO expression. The influence of IDO expression on survival was studied by multivariate Cox regression, adjusting for established clinical prognostic parameters. Real time PCR of tumor samples was performed in a subgroup of patients to analyse mRNA expression of IDO and INDOL-1. IDO high-expression was observed in 44.2% of OSCC patients. No significant correlation was found between IDO expression and clinical stage, sex, age, tumor site, tumor size, metastasis or tumor grade. The median overall survival time was 3.1 years for patients with IDO low tumors, compared to 1.36 years for IDO high tumors (P=.028). Subset analysis of patients receiving adjuvant radio-chemotherapy showed a significant difference (P=.0046) in overall survival between IDO low tumors (3.35 years) and IDO high tumors (1.26 years). In contrast, the impact of IDO expression on survival time in patients without adjuvant therapy was not significant (P=.574). Interestingly, INDOL-1 was not expressed in OSCC. IDO high expression represents a significant negative prognostic factor in patients with OSCC, especially in those patients undergoing adjuvant radiochemotherapy. Our data support the suggestion, co-administration of small-molecule IDO inhibitors could represent a promising new strategy to increase the anti-tumor activity of radio-chemotherapy in patients with IDO positive OSCC.
authors: Division of Maxillofacial Surgery, Innsbruck Medical University, Austria.
authors: Klaus
authors: K
authors: Laimer
authors: Birgit
authors: B
authors: Troester
authors: Frank
authors: F
authors: Kloss
authors: Georg
authors: G
authors: Schafer
authors: Peter
authors: P
authors: Obrist
authors: Alexander
authors: A
authors: Perathoner
authors: Johannes
authors: J
authors: Laimer
authors: Gerald
authors: G
authors: Brandacher
authors: Michael
authors: M
authors: Rasse
authors: Raimund
authors: R
authors: Margreiter
authors: Albert
authors: A
authors: Amberger
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D009363:Neoplasm Proteins / Q000378:metabolism*; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D009363:Neoplasm Proteins