Prognostic significance of TIE2-expressing monocytes in hilar cholangiocarcinoma

J Surg Oncol. 2016 Jul;114(1):91-8. doi: 10.1002/jso.24249. Epub 2016 Apr 25.

Abstract

Background and objectives: Angiopoietins (Angs) play a pivotal role in angiogenesis and inflammation, and are associated with prognosis in malignancies. Monocyte express Ang-receptor TIE2 and correlate with prognosis in cancer. We aimed to investigate the prognostic value of Angs and TIE2-expressing monocytes (TEMs) in cholangiocarcinoma.

Methods: We analyzed surgically resected tumor specimens of hilar cholangiocarcinoma (n = 47) for distribution of Angs (Ang 1/Ang 2) and TEMs, as defined by co-expression of CD14 and Ang receptor TIE2. Ang expression and abundance of TEMs were correlated with clinicopathologic characteristics, tumor recurrence and patients' survival.

Results: High Ang 1 expression correlated with reduced metastasis (P < 0.05). Patients characterized by invading Ang-receptor bearing TEMs in tumor showed lower tumor recurrence (P < 0.05). Furthermore, TEMs in tumor and tumor invasive front correlated with increased survival (P < 0.05). TEMs in tumor invasive front were confirmed as independent prognosticator in multivariate survival analysis (P < 0.05).

Conclusions: High Ang 1 expression in hilar cholangiocarcinoma and infiltration of TEMs defines a subgroup of patients with beneficial tumor characteristics and prolonged survival. Besides suggested functional links between Ang expression and recruitment of TEMs, our data have possible clinical implications as novel diagnostic tools. J. Surg. Oncol. 2016;114:91-98. © 2016 Wiley Periodicals, Inc.

Keywords: TIE2-expressing monocytes; angiopoietins; cholangiocarcinoma; liver resection; tumor associated macrophages.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Angiopoietin-1 / metabolism*
  • Angiopoietin-2 / metabolism*
  • Bile Duct Neoplasms / diagnosis*
  • Bile Duct Neoplasms / metabolism
  • Bile Duct Neoplasms / mortality
  • Bile Duct Neoplasms / surgery
  • Biomarkers, Tumor / metabolism*
  • Female
  • Follow-Up Studies
  • Hepatectomy
  • Hepatic Duct, Common* / pathology
  • Hepatic Duct, Common* / surgery
  • Humans
  • Klatskin Tumor / diagnosis*
  • Klatskin Tumor / metabolism
  • Klatskin Tumor / mortality
  • Klatskin Tumor / surgery
  • Male
  • Middle Aged
  • Monocytes / metabolism
  • Neoplasm Metastasis
  • Neoplasm Recurrence, Local / diagnosis
  • Neoplasm Recurrence, Local / metabolism
  • Prognosis
  • Receptor, TIE-2 / metabolism*
  • Survival Analysis

Substances

  • ANGPT1 protein, human
  • ANGPT2 protein, human
  • Angiopoietin-1
  • Angiopoietin-2
  • Biomarkers, Tumor
  • Receptor, TIE-2