Prognostic significance of TIE2-expressing monocytes in hilar cholangiocarcinoma.
OBJECTIVE
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.
Department of General, Visceral and Transplantation Surgery and Department of General, Visceral, Vascular and Thoracic Surgery, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Georgi
G
Atanasov
Department of Visceral-, Transplantation-, Thoracic- and Vascular Surgery, University Hospital Leipzig, Leipzig, Germany.
Hans-Michael
HM
Hau
Department of Visceral-, Transplantation-, Thoracic- and Vascular Surgery, University Hospital Leipzig, Leipzig, Germany.
Corinna
C
Dietel
Department of General, Visceral and Transplantation Surgery and Department of General, Visceral, Vascular and Thoracic Surgery, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Christian
C
Benzing
Department of General, Visceral and Transplantation Surgery and Department of General, Visceral, Vascular and Thoracic Surgery, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Felix
F
Krenzien
Department of General, Visceral and Transplantation Surgery and Department of General, Visceral, Vascular and Thoracic Surgery, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Andreas
A
Brandl
Department of General, Visceral and Transplantation Surgery and Department of General, Visceral, Vascular and Thoracic Surgery, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Julianna P
JP
Englisch
Department of Visceral-, Transplantation-, Thoracic- and Vascular Surgery, University Hospital Leipzig, Leipzig, Germany.
Georg
G
Wiltberger
Institute of Pathology, University Hospital Leipzig, Leipzig, Germany.
Katrin
K
Schierle
Transplant Institute and Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard University, Boston, Massachusetts.
Simon C
SC
Robson
Department of General, Visceral and Transplantation Surgery and Department of General, Visceral, Vascular and Thoracic Surgery, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Anja
A
Reutzel-Selke
Department of Hepato-Pancreato-Biliary Surgery, Nurnberg, Germany.
Sven
S
Jonas
Department of General, Visceral and Transplantation Surgery and Department of General, Visceral, Vascular and Thoracic Surgery, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Andreas
A
Pascher
Department of General, Visceral and Transplantation Surgery and Department of General, Visceral, Vascular and Thoracic Surgery, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Johann
J
Pratschke
Department of General, Visceral and Transplantation Surgery and Department of General, Visceral, Vascular and Thoracic Surgery, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Moritz
M
Schmelzle
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D042683:Angiopoietin-1 / Q000378:metabolism*; D042702:Angiopoietin-2 / Q000378:metabolism*; D001650:Bile Duct Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000401:mortality / Q000601:surgery; D014408:Biomarkers, Tumor / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D006498:Hepatectomy; D006500:Hepatic Duct, Common / Q000473:pathology / Q000601:surgery; D006801:Humans; D018285:Klatskin Tumor / Q000175:diagnosis* / Q000378:metabolism / Q000401:mortality / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis / Q000378:metabolism; D011379:Prognosis; D042787:Receptor, TIE-2 / Q000378:metabolism*; D016019:Survival Analysis
C467630:ANGPT1 protein, human; C586513:ANGPT2 protein, human; D042683:Angiopoietin-1; D042702:Angiopoietin-2; D014408:Biomarkers, Tumor; D042787:Receptor, TIE-2
TIE2-expressing monocytes; angiopoietins; cholangiocarcinoma; liver resection; tumor associated macrophages