Increased synthesis of indoleamine-2,3-dioxygenase protein is positively associated with impaired survival in patients with serous-type, but not with other types of, ovarian cancer

Abstract

We previously reported that indoleamine-2,3dioxygenase (IDO) is associated with paclitaxel resistance and that IDO serves as a marker of poor prognosis in ovarian serous adenocarcinomas (SA). In this study, to explore the role of IDO in the development of various histological types of ovarian cancer, we further examined IDO expression not only in SA but also in other types of ovarian cancers. Expression of IDO protein was analyzed by immunohistochemistry for a total of 122 ovarian cancers including 40 SA, 67 clear cell adenocarcinomas (CCA), and 15 endometrioid adenocarcinomas (EA) with informed consent. Among these cases, there were 11 CCA accompanied with endometriosis and 60 cases with lymph node metastasis. We classified the samples into four categories by IDO staining pattern. IDO staining was positive in 57.5% of SA, 49.2% of CCA, and 73.3% of EA, respectively. The Kaplan-Meier survival curve showed a clear relationship between staining score and overall survival for patients with advanced (stages III and IV) SA (n=33) who underwent optimal surgery and paclitaxelcarboplatin (TC) chemotherapy as a first-line regimen. There was no association between IDO staining score and overall survival in the CCA cases. Eight of 11 cases (72.7%) of CCA accompanied by endometriosis presented identical staining patterns of IDO between CCA and endometriosis. In 43 of 60 cases (71.6%) with lymph node metastasis, the staining patterns of IDO showed a correspondence between the primary lesion and metastatic site. These results suggested that the increased synthesis of IDO protein was positively associated with impaired survival only in the serous type of ovarian cancer.

Indoleamine 2,3-Dioxygenase Expression in Human Cancers: Clinical and Immunologic Perspectives

“…However, 21 out of 60 TDLNs analyzed had a high density of IDO þ cells, and these have been associated with a decreased 5-year survival rate (33). Finally, it has been observed that patients with ovarian carcinoma presenting high IDO expression, as evaluated by IHC (15) or global gene expression profiles (34,35), have a shorter postsurgery life expectancy. Only 2 studies have reported results contradictory to those discussed above.…”

Assessment of Tryptophan Uptake and Kinetics Using 1-(2-18F-Fluoroethyl)-l-Tryptophan and α-11C-Methyl-l-Tryptophan PET Imaging in Mice Implanted with Patient-Derived Brain Tumor Xenografts

“…In cancer, local tryptophan depletion, kynurenine, and other KP metabolites foster an immunosuppressive tumor microenvironment (5,6). Recent studies have identified IDO1 in both hematologic cancers and solid tumors (e.g., breast cancer, lung cancer, glioblastoma) (7) with increased IDO1 expression linked to poorer outcomes (8)(9)(10). In addition to IDO1, TDO2 may also play a prominent role in glioma pathophysiology (11,12).…”

Evaluation of the expression of the immunosuppressive enzyme – indoleamine 2,3-dioxygenase in ovarian cancer tissue

“…Wyraźną korelację między ekspresją IDO a krótszym czasem przeżycia u chorych z zaawansowanym surowiczym rakiem jajnika (nie z innymi typami histologicznymi) potwierdziły badania Takao i wsp. [16]. Inaba i wsp.…”