Indoleamine 2,3-dioxygenase expression predicts impaired survival of invasive cervical cancer patients treated with radical hysterectomy

Gynecol Oncol. 2010 Jun;117(3):423-8. doi: 10.1016/j.ygyno.2010.02.028. Epub 2010 Mar 28.


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.

MeSH terms

  • Analysis of Variance
  • Disease-Free Survival
  • Female
  • Humans
  • Hysterectomy
  • Immunohistochemistry
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / biosynthesis*
  • Lymph Node Excision
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Staging
  • Uterine Cervical Neoplasms / enzymology*
  • Uterine Cervical Neoplasms / pathology
  • Uterine Cervical Neoplasms / surgery*


  • Indoleamine-Pyrrole 2,3,-Dioxygenase