title: Relationship between indoleamine 2,3-dioxygenase activity and lymphatic invasion propensity of colorectal carcinoma.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Atilla Engin, Ahmet Karamercan, Department of General Surgery, Faculty of Medicine, Gazi University, TR 06500 Beşevler, Ankara, Turkey.
authors.forename: Atilla
authors.initials: A
authors.lastname: Engin
authors.affiliation: Atilla Engin, Ahmet Karamercan, Department of General Surgery, Faculty of Medicine, Gazi University, TR 06500 Beşevler, Ankara, Turkey.
authors.forename: Ipek Isik
authors.initials: II
authors.lastname: Gonul
authors.affiliation: Atilla Engin, Ahmet Karamercan, Department of General Surgery, Faculty of Medicine, Gazi University, TR 06500 Beşevler, Ankara, Turkey.
authors.forename: Ayse Basak
authors.initials: AB
authors.lastname: Engin
authors.affiliation: Atilla Engin, Ahmet Karamercan, Department of General Surgery, Faculty of Medicine, Gazi University, TR 06500 Beşevler, Ankara, Turkey.
authors.forename: Ahmet
authors.initials: A
authors.lastname: Karamercan
authors.affiliation: Atilla Engin, Ahmet Karamercan, Department of General Surgery, Faculty of Medicine, Gazi University, TR 06500 Beşevler, Ankara, Turkey.
authors.forename: Aylin
authors.initials: A
authors.lastname: Sepici Dincel
authors.affiliation: Atilla Engin, Ahmet Karamercan, Department of General Surgery, Faculty of Medicine, Gazi University, TR 06500 Beşevler, Ankara, Turkey.
authors.forename: Ayse
authors.initials: A
authors.lastname: Dursun
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis* / Q000097:blood / Q000652:urine; D001708:Biopterins / Q000652:urine; D002277:Carcinoma / Q000097:blood / Q000201:enzymology* / Q000556:secondary* / Q000652:urine; D016022:Case-Control Studies; D002851:Chromatography, High Pressure Liquid; D015179:Colorectal Neoplasms / Q000097:blood / Q000201:enzymology* / Q000473:pathology* / Q000652:urine; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000032:analysis* / Q000097:blood; D007737:Kynurenine / Q000097:blood; D008207:Lymphatic Metastasis; D008208:Lymphatic System / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D019798:Neopterin / Q000652:urine; D011237:Predictive Value of Tests; D014364:Tryptophan / Q000097:blood; D016482:Urinalysis
chemical_list: D014408:Biomarkers, Tumor; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D001708:Biopterins; D007737:Kynurenine; D019798:Neopterin; D014364:Tryptophan
keywords: Colorectal carcinoma; Indoleamine-2,3-dioxygen; Lymph node metastasis; Lymphovascular invasion; Tryptophan