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: Kei Asukai, Koichi Kawamoto, Hidetoshi Eguchi, Masamitsu Konno, Naohiro Nishida, Jun Koseki, Kozo Noguchi, Shinichiro Hasegawa, Hisataka Ogawa, Daisaku Yamada, Yoshito Tomimaru, Akira Tomokuni, Tadafumi Asaoka, Takehiro Noda, Hiroshi Wada, Kunihito Gotoh, Shigeru Marubashi, Hiroaki Nagano, Yuichiro Doki, Masaki Mori, Hideshi Ishii
• Journal: Annals of surgical oncology (Ann Surg Oncol) Vol. 22 Suppl 3 Pg. S1524-31 (Dec 2015) ISSN: 1534-4681 [Electronic] United States
• PMID: 26228109 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor
• IL17RA protein, human
• IL6 protein, human
• Inflammation Mediators
• Interleukin-17
• Interleukin-6
• Receptors, Interleukin-17

Topics

• Bile Duct Neoplasms (metabolism, pathology, surgery)
• Biomarkers, Tumor (metabolism)
• Cholangiocarcinoma (metabolism, pathology, surgery)
• Enzyme-Linked Immunosorbent Assay
• Female
• Follow-Up Studies
• Humans
• Immunoenzyme Techniques
• Inflammation Mediators (metabolism)
• Interleukin-17 (metabolism)
• Interleukin-6 (metabolism)
• Male
• Middle Aged
• Neoplasm Recurrence, Local (metabolism, pathology, surgery)
• Neoplasm Staging
• Prognosis
• Receptors, Interleukin-17 (metabolism)
• Survival Rate