Case Control Study
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 7, 2016; 22(13): 3592-3601
Published online Apr 7, 2016. doi: 10.3748/wjg.v22.i13.3592
Relationship between indoleamine 2,3-dioxygenase activity and lymphatic invasion propensity of colorectal carcinoma
Atilla Engin, Ipek Isik Gonul, Ayse Basak Engin, Ahmet Karamercan, Aylin Sepici Dincel, Ayse Dursun
Atilla Engin, Ahmet Karamercan, Department of General Surgery, Faculty of Medicine, Gazi University, TR 06500 Beşevler, Ankara, Turkey
Ipek Isik Gonul, Ayse Dursun, Department of Pathology, Faculty of Medicine, Gazi University, TR 06500 Beşevler, Ankara, Turkey
Ayse Basak Engin, Department of Toxicology, Faculty of Pharmacy, Gazi University, TR 06330 Hipodrom, Ankara, Turkey
Aylin Sepici Dincel, Department of Biochemistry, Faculty of Medicine, Gazi University, TR 06500 Beşevler, Ankara, Turkey
Author contributions: Engin A designed and co-ordinated the study, selected the patients, did surgical interventions and wrote the manuscript; Gonul II and Dursun A did the immunohistochemical staining and analysis; Karamercan A involved in surgical interventions; Engin AB and Sepici Dincel A performed the experiments; and Engin AB involved in editing the manuscript.
Supported by Gazi University, Scientific Research Projects Division, No. 01/2007-62.
Institutional review board statement: The study was approved by Gazi University, Local Ethics Committee.
Informed consent statement: All participants’ rights were protected and informed consents were obtained according to the Helsinki Declaration.
Conflict-of-interest statement: The authors declare no conflict of interest.
Data sharing statement: Participants gave informed consent for data sharing.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Dr. Ayse Basak Engin, Associate Professor, Department of Toxicology, Faculty of Pharmacy, Gazi University, TR 06330 Hipodrom, Ankara, Turkey. abengin@gmail.com
Telephone: +90-312-2023084 Fax: +90-312-2222326
Received: September 11, 2015
Peer-review started: September 14, 2015
First decision: January 13, 2016
Revised: January 31, 2016
Accepted: March 2, 2016
Article in press: March 2, 2016
Published online: April 7, 2016
Abstract

AIM: To evaluate whether serum and tumor indoleamine 2,3-dioxygenase activities can predict lymphatic invasion (LI) or lymph node metastasis in colorectal carcinoma.

METHODS: The study group consisted of 44 colorectal carcinoma patients. The patients were re-grouped according to the presence or absence of LI and lymph node metastasis. Forty-three cancer-free subjects without any metabolic disturbances were included into the control group. Serum neopterin was measured by enzyme linked immunosorbent assay. Urinary neopterin and biopterin, serum tryptophan (Trp) and kynurenine (Kyn) concentrations of all patients were determined by high performance liquid chromatography. Kyn/Trp was calculated and its correlation with serum neopterin was determined to estimate the serum indoleamine 2,3-dioxygenase activity. Tissue sections from the studied tumors were re-examined histopathologically and were stained by immunohistochemistry with indoleamine-2,3-dioxygenase antibodies.

RESULTS: Neither serum nor urinary neopterin was significantly different between the patient and control groups (both P > 0.05). However, colorectal carcinoma patients showed a significant positive correlation between the serum neopterin levels and Kyn/Trp (r = 0.450, P < 0.01). Urinary biopterin was significantly higher in cancer cases (P < 0.05). Serum Kyn/Trp was significantly higher in colorectal carcinoma patients (P < 0.01). Lymphatic invasion was present in 23 of 44 patients, of which only 12 patients had lymph node metastasis. Eleven patients with LI had no lymph node metastasis. Indoleamine-2,3-dioxygenase intensity score was significantly higher in LI positive cancer group (44.56% ± 6.11%) than negative colorectal cancer patients (24.04% ± 6.90%), (P < 0.05). Indoleamine 2,3-dioxygenase expression correlated both with the presence of LI and lymph node metastasis (P < 0.01 and P < 0.05, respectively). A significant difference between the accuracy of diagnosis by using either total indoleamine-2,3-dioxygenase immunostaining score or of lymph node metastasis was found during the evaluation of cancer patients.

CONCLUSION: Indoleamine-2,3-dioxygenase expression may predict the presence of unrecognized LI and lymph node metastasis and may be included in the histopathological evaluation of colorectal carcinoma cases.

Keywords: Colorectal carcinoma, Tryptophan, Indoleamine-2,3-dioxygen, Lymphovascular invasion, Lymph node metastasis

Core tip: Colorectal cancer (CRC) is one of the major public health problems in the world. Clinicopathological findings of patients who died of recurrent CRC after resection revealed that approximately 14% of patients with lymph node negative CRC die because of the presence of unrecognizable tumor cells that are categorized as micrometastases. Tryptophan degrading enzyme, indoleamine-2,3-dioxygenase expression by tumor cells has been shown to be correlated with a poor clinical prognosis of colon cancer. Our data indicated that high total indoleamine-2,3-dioxygenase immunostaining score is a strong predictor for immune tolerance, lymphatic invasion and subsequent lymph node metastasis. Therefore, indoleamine-2,3-dioxygenase immunostaining might be recommended for histopathological evaluation of CRC cases.