title: Prognostic Impact of Peritumoral IL-17-Positive Cells and IL-17 Axis in Patients with Intrahepatic Cholangiocarcinoma.
abstract: BACKGROUND
  Development of cancer has been linked to inflammatory cytokines such as interleukin (IL)-6 and IL-17. In this study, we assessed the expression of these cytokines in intrahepatic cholangiocarcinoma (ICC) and determined their correlation to the survival probability.
  
  
  METHODS
  A total of 72 consecutive patients who underwent curative resection of ICC at Osaka University Hospital from March 1998 to November 2014 were enrolled. Immunohistochemical analysis was performed for IL-17 and its receptor A (IL-17RA), as well as IL-6. Enzyme-linked immunosorbent assay (ELISA) was performed for preoperative plasma levels of IL-6 and IL-17 in 32 patients with ICC.
  
  
  RESULTS
  Immunohistochemical analysis showed that the IL-6(high) (n = 34) and IL-17RA(high) (n = 29) groups had significantly worse disease-free survival (DFS) than IL-6(low) (n = 38) and IL-17RA(low) (n = 43) groups, respectively. Although IL-17(+) cells were abundant in the intratumoral area, patients with high peritumoral, but not intratumoral, IL-17(+) cells (n = 28) corresponded with a significantly lower overall survival (OS) and DFS (OS, p = 0.023; DFS, p = 0.026) than those with low group. Moreover, multivariate Cox proportional hazards analysis revealed that IL-6, peritumoral IL-17(+), and IL-17RA are independent prognostic factors for DFS (p = 0.023, p = 0.0088, p = 0.039, respectively). In addition, high preoperative plasma levels of IL-6 in patients with ICC corresponded with significantly lower DFS (p = 0.002).
  
  
  CONCLUSIONS
  Our data suggested that IL-6, peritumoral IL-17(+) cells, and IL-17RA expression are postoperative useful markers for predicting recurrence in patients with ICC.
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Asukai
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.|Department of Frontier Science for Cancer and Chemotherapy, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Kawamoto
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Eguchi
authors.affiliation: Department of Frontier Science for Cancer and Chemotherapy, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Konno
authors.affiliation: Department of Frontier Science for Cancer and Chemotherapy, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
authors.forename: Naohiro
authors.initials: N
authors.lastname: Nishida
authors.affiliation: Department of Cancer Profiling Discovery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Koseki
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
authors.forename: Kozo
authors.initials: K
authors.lastname: Noguchi
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Hasegawa
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
authors.forename: Hisataka
authors.initials: H
authors.lastname: Ogawa
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
authors.forename: Daisaku
authors.initials: D
authors.lastname: Yamada
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Tomimaru
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Tomokuni
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
authors.forename: Tadafumi
authors.initials: T
authors.lastname: Asaoka
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
authors.forename: Takehiro
authors.initials: T
authors.lastname: Noda
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Wada
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
authors.forename: Kunihito
authors.initials: K
authors.lastname: Gotoh
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Marubashi
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.|Department of Surgery, Graduate School of Medicine, Yamaguchi University, Ube City, Yamaguchi, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Nagano
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Doki
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan. mmori@gesurg.med.osaka-u.ac.jp.
authors.forename: Masaki
authors.initials: M
authors.lastname: Mori
authors.affiliation: Department of Frontier Science for Cancer and Chemotherapy, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan. hishii@gesurg.med.osaka-u.ac.jp.|Department of Cancer Profiling Discovery, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan. hishii@gesurg.med.osaka-u.ac.jp.
authors.forename: Hideshi
authors.initials: H
authors.lastname: Ishii
mesh_terms: D001650:Bile Duct Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D014408:Biomarkers, Tumor / Q000378:metabolism; D018281:Cholangiocarcinoma / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D018836:Inflammation Mediators / Q000378:metabolism*; D020381:Interleukin-17 / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D009367:Neoplasm Staging; D011379:Prognosis; D053722:Receptors, Interleukin-17 / Q000378:metabolism*; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; C109985:IL17RA protein, human; C508600:IL6 protein, human; D018836:Inflammation Mediators; D020381:Interleukin-17; D015850:Interleukin-6; D053722:Receptors, Interleukin-17