TY - JOUR
T1 - Expression and prognostic impact of indoleamine 2,3-dioxygenase in oral squamous cell carcinomas
AU - Laimer, Klaus
AU - Troester, Birgit
AU - Kloss, Frank
AU - Schafer, Georg
AU - Obrist, Peter
AU - Perathoner, Alexander
AU - Laimer, Johannes
AU - Brandacher, Gerald
AU - Rasse, Michael
AU - Margreiter, Raimund
AU - Amberger, Albert
N1 - Funding Information:
The authors would like to thank Mr. Martin Heitz for excellent technical assistance. This work was supported by grants from the “Österreichische Krebshilfe/Tirol and the “Österreichische Gesellschaft für chirurgische Onkologie (ACO-ASSO)”.
PY - 2011/5
Y1 - 2011/5
N2 - 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.
AB - 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.
KW - IDO
KW - INDOL-1
KW - Oral squamous cell carcinoma
KW - Prognosis
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U2 - 10.1016/j.oraloncology.2011.03.007
DO - 10.1016/j.oraloncology.2011.03.007
M3 - Article
C2 - 21440489
AN - SCOPUS:79956200606
SN - 1368-8375
VL - 47
SP - 352
EP - 357
JO - Oral Oncology
JF - Oral Oncology
IS - 5
ER -