Angiogenic inflammation and formation of necrosis in the tumor microenvironment influence patient survival after radical surgery for de novo hepatocellular carcinoma in non-cirrhosis

Abstract

Abstract Background Tumor escape mechanisms mediated in the tumor microenvironment can significantly reduce the capacity of the anti-tumor function of the immune system. TIE2-expressing monocytes (TEMs), related angiopoietins, and tumor necrosis are considered to have a key role in this process. We aimed to investigate the abundance and clinical significance of these biomarkers in hepatocellular carcinoma (HCC). Methods In this retrospective study, 58 HCC patients received surgery with a curative intent. The abundance of TEMs, angiopoietin-1 and -2 were detected in tumor specimens of the HCC patients (n = 58), and together with the occurrence of histologic tumor necrosis, were associated with established clinicopathological characteristics and survival. Results Patients with HCC characterized by necrosis and TEMs revealed reduced both overall survival and recurrence-free survival (all p < 0.05). Angiopoietins and TEMs were associated with metastatic and recurrent HCC. Furthermore, the formation of histologic tumor necrosis was associated with advanced tumor stage and density of TEMs (all p < 0.05). Conclusions Histologic tumor necrosis, TEMs, and related angiopoietins were associated with multiple HCC parameters and patient survival. The tumor necrosis–TEM–angiopoietin axis may offer a novel diagnostic modality to predict patient outcome after surgery for HCC.

Keywords

• Hepatocellular carcinoma
• Tumor-infiltrating macrophages
• TIE2-expressing monocytes
• Tumor necrosis
• Angiopoietins
• Angiogenesis