Cholangiocarcinoma-associated macrophages and tumor necrosis impact survival after surgery

Abstract

Background: Tumor necrosis as well as tumor-associated macrophages (TAMs) in tumor invasive front (TIF) have been suggested to have a prognostic value in 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. TAMs, tumor necrosis and grade of fibrosis were assessed immunohistochemically and histologically and correlated with clinicopathological characteristics, tumor recurrence, and patients’ survival. Results: Patients with tumors characterized by necrosis or low CD68 density showed a significantly decreased recurrence-free and overall survival. Patients with high density of TAMs in TIF or absence of necrosis showed significantly lower incidence of tumor recurrence (both ρ < 0.05). Absence of tumor necrosis and TAMs in TIF were confirmed as independent prognostic variables in a multivariate analysis (all ρ < 0.05). Conclusion: High levels of TAMs in TIF or absence of tumor necrosis is associated with a significantly improved recurrence free and overall survival. These Results suggest TAMs and necrosis as valuable prognostic markers in routine histopathologic evaluation, and might indicate more individualized therapeutic strategies.