Prognostic significance of macrophage invasion in hilar cholangiocarcinoma

Abstract

BackgroundTumor-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.MethodsWe 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.ResultsPatients 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).ConclusionsOverall 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.

Prognostic significance of TIE2‐expressing monocytes in hilar cholangiocarcinoma

“…Follow‐up after resection, overall and recurrence‐free survival rates of the study population have been previously described in detail . In summary, overall 1‐, 3‐ and 5‐year survival of our cohort was 78.8%, 51.4%, and 31.7%, respectively.…”

“…Histological diagnosis of the primary tumor stage and nodal status were determined by hematoxylin and eosin (H&E) stained sections. The clinicopathological characteristics of the study have been described in detail elsewhere .…”

Tumor reactive stroma in cholangiocarcinoma: The fuel behind cancer aggressiveness

“…Consistently, immunohistochemical analyses in Opisthorchis viverrini -associated CCA in a hamster model revealed a progressive, dramatic increase in M2 macrophages through carcinogenesis[28]. Studies from different groups showed that a high density of TAMs at the invasive front correlated with poor survival of CCA patients after resection[64,68,69]. However, it is important to underline that not all of these studies provided evidence that the observed TAM actually exhibited the pro-neoplastic, M2 phenotype.…”

“…However, it is important to underline that not all of these studies provided evidence that the observed TAM actually exhibited the pro-neoplastic, M2 phenotype. Whereas Subimerb et al[68] evaluated the expression of MAC387, a marker of recently infiltrated, bone marrow-derived, macrophages, Atanasov et al[69] evaluated the expression of resident, CD68 + macrophages. On the contrary, Hasita et al[64] sought to distinguish M2 TAMs from total resident macrophages based on their expression of CD163, in order to highlight their specific contribution to tumor progression.…”

Reduced EBP50 expression levels are correlated with unfavorable clinicopathological features of extrahepatic bile duct carcinoma and promote the proliferation and migration of QBC939 cells

“…Cell migration and invasion are also implicated in the development of tumors (19,20). Therefore, the potential of EBP50 knockdown to promote cell migration was investigated.…”