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. 2017 Jun 28;6(8):e1331806.
doi: 10.1080/2162402X.2017.1331806. eCollection 2017.

Tumor necrosis and infiltrating macrophages predict survival after curative resection for cholangiocarcinoma

Georgi Atanasov  1 , Corinna Dietel  2 , Linda Feldbrügge  1 , Christian Benzing  1 , Felix Krenzien  1 , Andreas Brandl  1 , Elli Mann  1 , Julianna Paulina Englisch  1 , Katrin Schierle  3 , Simon C Robson  4 , Katrin Splith  1 , Mehmet Haluk Morgul  1 , Anja Reutzel-Selke  1 , Sven Jonas  5 , Andreas Pascher  1 , Marcus Bahra  1 , Johann Pratschke  1 , Moritz Schmelzle  1
Affiliations

Tumor necrosis and infiltrating macrophages predict survival after curative resection for cholangiocarcinoma

Georgi Atanasov et al. Oncoimmunology. .

Abstract

Background. Tumor necrosis as well as tumor-associated macrophages (TAMs) in the tumor invasive front (TIF) have been suggested to have a prognostic value in selected solid tumors, inclusive hilar cholangiocarcinoma. However, little is known regarding their influence on tumor progression and prognosis in intrahepatic cholangiocarcinoma (iCC). Methods. We analyzed surgically resected tumor specimens of human iCC (n = 88) for distribution and localization of TAMs, as defined by expression of CD68, formation of necrosis and extent of peritumoral fibrosis. Abundance of TAMs, tumor necrosis and grade of fibrosis were assessed immunohistochemically and histologically and correlated with clinicopathological characteristics, tumor recurrence and patients' survival. Statistical analysis was performed using SPSS software. Results. Patients with tumors characterized by low levels of TAMs in TIF or necrosis showed a significantly decreased 1-, 3- and 5-y recurrence-free survival and a significantly decreased overall survival, when compared with patients with tumors showing high levels of TAMs in TIF or no necrosis. Patients with high density of TAMs in TIF showed significantly lower incidence of tumor recurrence, as well (p < 0.05). Absence of tumor necrosis and TAMs in TIF were confirmed as independent prognostic variables in the multivariate survival analysis (all p < 0.05). Conclusions. High levels of TAMs in TIF or absence of histologic tumor necrosis are associated with a significantly improved recurrence-free and overall survival of patients with iCC. These results suggest TAMs and necrosis as valuable prognostic markers in routine histopathologic evaluation, and might indicate more individualized therapeutic strategies.

Keywords: CD68; Intrahepatic cholangiocarcinoma; TAMs; Tumor associated macrophages; fibrosis; patient outcome; prognosis; tumor necrosis.

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Figures

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Overall survival and recurrence-free survival of the patients included in the study.
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Figure 2.
Figure 2.
(A) Intrahepatic cholangiocarcinoma stained with mAb CD68 PG-M1 with a high abundance of TAMs in tumor central area (TCA). Original magnification: x 200. (B) Intrahepatic cholangiocarcinoma stained with mAb CD68 PG-M1 with a high abundance of TAMs in tumor-infiltrating front (TIF). Original magnification: x 200. (C, D) Histological tumor specimen with (C) necrosis and (D) fibrosis. *Vital tumor cell formations, +Tumor necrosis, #Tumor fibrosis.
See this image and copyright information in PMC

References

    1. Takeya M, Komohara Y. Role of tumor-associated macrophages in human malignancies: Friend or foe? Pathol Int 2016; 66:491-505; PMID:27444136; https://doi.org/10.1111/pin.12440 - DOI - PubMed
    1. Lewis CE, Pollard JW. Distinct role of macrophages in different tumor microenvironments. Cancer Res 2006; 66(2):605-12; PMID:16423985; https://doi.org/10.1158/0008-5472.CAN-05-4005 - DOI - PubMed
    1. Mantovani A, Sozzani S, Locati M, Allavena P, Sica A. Macrophage polari- zation: Tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes. Trends Immunol 2002; 23(11):549-55; PMID:12401408; https://doi.org/10.1016/S1471-4906(02)02302-5 - DOI - PubMed
    1. Raggi C, Correnti M, Sica A, Andersen JB, Cardinale V, Alvaro D, Chiorino G, Forti E, Glaser S, Alpini G et al.. Cholangiocarcinoma stem-like subset shapes tumor-initiating niche by educating associated macrophages. J Hepatol 2017; 66(1):102-15; PMID:27593106; https://doi.org/10.1016/j.jhep.2016.08.012 - DOI - PMC - PubMed
    1. Lewis CE, Harney AS, Pollard JW. The multifaceted role of perivascular macrophages in tumors. Cancer Cell 2016; 30(1):18-25; PMID:27411586; https://doi.org/10.1016/j.ccell.2016.05.017 - DOI - PMC - PubMed

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