Prognostic role of indoleamine 2,3-dioxygenase in endometrial carcinoma.
OBJECTIVE
Indoleamine-2,3-dioxygenase (IDO) suppresses the function of T-lymphocytes and is an important immune escape mechanism for cancer. Therefore, it is to be expected that IDO influences prognosis of cancer patients. This study aimed to investigate the prognostic role of IDO expression in a large cohort of endometrial carcinoma (EC) patients.


METHODS
A tissue microarray containing primary EC tissue of 355 patients treated in a single institution was used to evaluate IDO expression. Expression of IDO was associated with clinicopathological characteristics, survival and previously determined numbers of CD8(+) and Foxp3(+) T-lymphocytes.


RESULTS
IDO(high) expression was associated with lower numbers of intratumoral CD8(+) T-lymphocytes (p=0.031). Next to well-known prognostic parameters, IDO(high) expression was independently associated with poor disease specific survival in the general cohort of EC patients (HR 2.62, 95% C.I. 1.48-4.66, p=0.001) and among patients with early stage EC (HR 3.06, 95% C.I. 1.10-8.54, p=0.032).


CONCLUSIONS
Our results show that IDO expression is associated with poor survival. This provides evidence that further research into the use of IDO blocking agents in cancer treatment is valid where it might be a promising new therapeutic strategy.
University of Groningen, University Medical Center Groningen, Department of Gynecologic Oncology, P.O. Box 30.001, 9700 RB Groningen, The Netherlands.
Renske A
RA
de Jong
Ido P
IP
Kema
Annemarie
A
Boerma
H Marike
HM
Boezen
Johannes J L
JJ
van der Want
Marloes J M
MJ
Gooden
Harry
H
Hollema
Hans W
HW
Nijman
D000368:Aged; D018414:CD8-Positive T-Lymphocytes; D002277:Carcinoma / Q000201:enzymology* / Q000276:immunology* / Q000473:pathology; D045744:Cell Line, Tumor; D016001:Confidence Intervals; D018572:Disease-Free Survival; D016889:Endometrial Neoplasms / Q000201:enzymology* / Q000276:immunology* / Q000473:pathology; D005260:Female; D051858:Forkhead Transcription Factors; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000378:metabolism*; D018655:Lymphocyte Count; D008875:Middle Aged; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness; D016017:Odds Ratio; D016016:Proportional Hazards Models; D013601:T-Lymphocytes
C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase