Prognostic significance of macrophage invasion in hilar cholangiocarcinoma.
BACKGROUND
Tumor-associated macrophages (TAMs) promote tumor progression and have an effect on survival in human cancer. However, little is known regarding their influence on tumor progression and prognosis in human hilar cholangiocarcinoma.


METHODS
We analyzed surgically resected tumor specimens of hilar cholangiocarcinoma (n = 47) for distribution and localization of TAMs, as defined by expression of CD68. Abundance of TAMs was correlated with clinicopathologic characteristics, tumor recurrence and patients' survival. Statistical analysis was performed using SPSS software.


RESULTS
Patients with high density of TAMs in tumor invasive front (TIF) showed significantly higher local and overall tumor recurrence (both ρ < 0.05). Furthermore, high density of TAMs was associated with decreased overall (one-year 83.6% vs. 75.1%; three-year 61.3% vs. 42.4%; both ρ < 0.05) and recurrence-free survival (one-year 93.9% vs. 57.4%; three-year 59.8% vs. 26.2%; both ρ < 0.05). TAMs in TIF and tumor recurrence, were confirmed as the only independent prognostic variables in the multivariate survival analysis (all ρ < 0.05).


CONCLUSIONS
Overall survival and recurrence free survival of patients with hilar cholangiocarcinoma significantly improved in patients with low levels of TAMs in the area of TIF, when compared to those with a high density of TAMs. These observations suggest their utilization as valuable prognostic markers in routine histopathologic evaluation, and might indicate future therapeutic approaches by targeting TAMs.
Department of General, Visceral and Transplantation Surgery and Department of General, Visceral, Vascular and Thoracic Surgery, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany. georgi.atanasov@charite.de.
Georgi
G
Atanasov
Department of Visceral-, Transplantation-, Thoracic- and Vascular Surgery, University Hospital Leipzig, Leipzig, Germany. hansmichael.hau@medizin.uni-leipzig.de.
Hans-Michael
HM
Hau
Department of Visceral-, Transplantation-, Thoracic- and Vascular Surgery, University Hospital Leipzig, Leipzig, Germany. corinna.dietel@gmx.de.
Corinna
C
Dietel
Department of General, Visceral and Transplantation Surgery and Department of General, Visceral, Vascular and Thoracic Surgery, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany. christian.benzing@charite.de.
Christian
C
Benzing
Department of General, Visceral and Transplantation Surgery and Department of General, Visceral, Vascular and Thoracic Surgery, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany. felix.krenzien@charite.de.
Felix
F
Krenzien
Department of General, Visceral and Transplantation Surgery and Department of General, Visceral, Vascular and Thoracic Surgery, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany. andreas.brandl@charite.de.
Andreas
A
Brandl
Department of Visceral-, Transplantation-, Thoracic- and Vascular Surgery, University Hospital Leipzig, Leipzig, Germany. georg.wiltberger@medizin.uni-leipzig.de.
Georg
G
Wiltberger
Department of Visceral-, Transplantation-, Thoracic- and Vascular Surgery, University Hospital Leipzig, Leipzig, Germany. ivan.matia@medizin.uni-leipzig.de.
Ivan
I
Matia
Department of Visceral-, Transplantation-, Thoracic- and Vascular Surgery, University Hospital Leipzig, Leipzig, Germany. isi.prager@hotmail.de.
Isabel
I
Prager
Institute of Pathology, University Hospital Leipzig, Leipzig, Germany. katrin.schierle@medizin.uni-leipzig.de.
Katrin
K
Schierle
The Transplant Institute and Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard University, Boston, MA, USA. srobson@bidmc.harvard.edu.
Simon C
SC
Robson
Department of General, Visceral and Transplantation Surgery and Department of General, Visceral, Vascular and Thoracic Surgery, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany. anja.reutzel-selke@charite.de.
Anja
A
Reutzel-Selke
Department of General, Visceral and Transplantation Surgery and Department of General, Visceral, Vascular and Thoracic Surgery, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany. johann.pratschke@charite.de.
Johann
J
Pratschke
Department of General, Visceral and Transplantation Surgery and Department of General, Visceral, Vascular and Thoracic Surgery, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany. moritz.schmelzle@charite.de.|Translational Centre for Regenerative Medicine, Leipzig University, Leipzig, Germany. moritz.schmelzle@charite.de.
Moritz
M
Schmelzle
Centre Hépato-Biliaire, Université Paris Sud, Hôpital Paul Brousse, Paris, France. svnjns@gmail.com.
Sven
S
Jonas
D000368:Aged; D015703:Antigens, CD / Q000096:biosynthesis*; D015214:Antigens, Differentiation, Myelomonocytic / Q000096:biosynthesis*; D001650:Bile Duct Neoplasms / Q000175:diagnosis* / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D018285:Klatskin Tumor / Q000175:diagnosis* / Q000378:metabolism* / Q000401:mortality; D008264:Macrophages / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology; D011379:Prognosis; D015996:Survival Rate / Q000639:trends; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; C067980:CD68 antigen, human; D000097382:CD68 Molecule