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: Tomoko Inaba, Kazuhiko Ino, Hiroaki Kajiyama, Kiyosumi Shibata, Eiko Yamamoto, Shinji Kondo, Tomokazu Umezu, Akihiro Nawa, Osamu Takikawa, Fumitaka Kikkawa
• Journal: Gynecologic oncology (Gynecol Oncol) Vol. 117 Issue 3 Pg. 423-8 (Jun 2010) ISSN: 1095-6859 [Electronic] United States
• PMID: 20350764 (Publication Type: Journal Article)
• Copyright: Copyright 2010 Elsevier Inc. All rights reserved.

Chemical References

• Indoleamine-Pyrrole 2,3,-Dioxygenase

Topics

• 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, pathology, surgery)