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. 2015 Oct 24:15:790.
doi: 10.1186/s12885-015-1795-7.

Prognostic significance of macrophage invasion in hilar cholangiocarcinoma

Georgi Atanasov  1 , Hans-Michael Hau  2 , Corinna Dietel  3 , Christian Benzing  4 , Felix Krenzien  5 , Andreas Brandl  6 , Georg Wiltberger  7 , Ivan Matia  8 , Isabel Prager  9 , Katrin Schierle  10 , Simon C Robson  11 , Anja Reutzel-Selke  12 , Johann Pratschke  13 , Moritz Schmelzle  14   15 , Sven Jonas  16
Affiliations

Prognostic significance of macrophage invasion in hilar cholangiocarcinoma

Georgi Atanasov et al. BMC Cancer. .

Abstract

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.

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Figures

Fig. 1
Fig. 1
a Overall survival after surgery for hilar cholangiocarcinoma (n = 47). b Overall survival after surgery for hilar cholangiocarcinoma (n = 37) according to R status. c Overall survival after surgery referred to CD68-positve TAMs in the tumor infiltration front (TIF) regardless of R status (n = 47). d Overall survival after surgery referred to TAMs in the tumor infiltration front (TIF) after R0 resection (n = 37). e Recurrence-free survival of all patients after surgery for hilar cholangiocarcinoma (n = 47). f Recurrence-free survival after surgery correlated to TAMs in the tumor invasive front (TIF) regardless of R status (n = 47). g Recurrence-free survival correlated to TAMs in the tumor invasive front (TIF) following R0 surgery (n = 37)
Fig. 2
Fig. 2
a CD68-positive macrophages in normal liver tissue. Normal liver parenchyma revealed a homogenous infiltration pattern with no preference for perivascular areas or clumping of TAMs. Original magnification: x 200; scale bar = 50 μm. b Hilar cholangiocarcinoma stained with mAb CD68 PG-M1 with a high abundance of TAMs (tumorous tissue “TT” score 3). Original magnification: x 200; scale bar = 50 μm. c Tumor infiltration front (TIF) positive for CD68-positive TAMs (TIF score 2 / high abundance / positive). Original magnification: x 200; scale bar = 50 μm
See this image and copyright information in PMC

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