title: Indoleamine 2,3-dioxygenase expression predicts impaired survival of invasive cervical cancer patients treated with radical hysterectomy.
abstract: OBJECTIVE
  Indoleamine 2,3-dioxygenase (IDO) is a tryptophan-catabolizing enzyme that induces tolerance to host immune surveillance within the tumor microenvironment. The present study aimed to investigate IDO expression and its prognostic significance in invasive cervical cancer.
  
  
  METHODS
  Immunohistochemical expression of IDO in tumor tissues and its association with clinicopathological factors and survival were analyzed in 112 stage IB-IIB cervical cancer patients treated with radical hysterectomy and pelvic lymphadenectomy.
  
  
  RESULTS
  IDO was diffusely expressed in tumor cells in 29 (26%) cases and focally expressed at the invasive front in 29 (26%) cases, while the other 54 (48%) cases were IDO-negative. IDO expression was positively correlated with clinical stage, lymph node metastasis, and lymph-vascular space invasion, but not with histological type. Patients with diffuse IDO expression had significantly reduced overall survival (OS) and disease-free survival (DFS) compared to patients with no IDO expression. The 5-year OS/DFS rates for the IDO-negative, focally positive, and diffusely positive groups were 92.3%/84.9%, 89.5%/75.8%, and 65.5%/51.7%, respectively. When we analyzed patients with stage IB disease alone (n=67), the OS and DFS for the IDO-diffusely positive group were significantly lower than those for the IDO-negative group. In multivariate analysis, diffuse IDO expression was found to be an independent prognostic factor for impaired OS and DFS.
  
  
  CONCLUSIONS
  Diffuse expression of IDO in the tumor obtained from Stage IB-IIB cervical cancer patients who underwent radical hysterectomy was correlated with an unfavorable clinical outcome. These findings suggest that IDO may be a novel post-operative prognostic indicator for stage IB-IIB cervical cancer.
authors.affiliation: Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Inaba
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Ino
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kajiyama
authors.forename: Kiyosumi
authors.initials: K
authors.lastname: Shibata
authors.forename: Eiko
authors.initials: E
authors.lastname: Yamamoto
authors.forename: Shinji
authors.initials: S
authors.lastname: Kondo
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Umezu
authors.forename: Akihiro
authors.initials: A
authors.lastname: Nawa
authors.forename: Osamu
authors.initials: O
authors.lastname: Takikawa
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Kikkawa
mesh_terms: D000704:Analysis of Variance; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007044:Hysterectomy; D007150:Immunohistochemistry; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000096:biosynthesis*; D008197:Lymph Node Excision; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D002583:Uterine Cervical Neoplasms / Q000201:enzymology* / Q000473:pathology / Q000601:surgery*
chemical_list: D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase