Affiliation:
1. Department of Pathology Cancer Institute Hospital Japanese Foundation for Cancer Research (JFCR) Tokyo Japan
2. Division of Pathology Cancer Institute JFCR Tokyo Japan
3. Department of Diagnostic Pathology Kumamoto University Hospital Chuo‐ku Japan
4. Department of Pathology Saitama Cancer Center Ina Japan
5. Division of Hepatobiliary and Pancreatic Surgery Cancer Institute Hospital JFCR Tokyo Japan
6. Department of Pathology Toranomon Hospital Tokyo Japan
7. Pathology Project for Molecular Targets Cancer Institute JFCR Tokyo Japan
Abstract
AbstractAimVessels encapsulating tumor clusters (VETC) represents an adverse prognostic morphological feature of hepatocellular carcinoma (HCC), which is associated with an immunosuppressive tumor immune microenvironment (TIM). However, the underlying factors characterizing the TIM in HCC with a VETC pattern (VETC‐positive HCC) remain uncertain. Oncostatin M (OSM), a pleiotropic cytokine of the interleukin‐6 family, regulates various biological processes, including inflammation, proliferation, and invasiveness of tumor cells. We aimed to test a hypothesis that OSM is associated with the immunosuppressive TIM of VETC‐positive HCC.MethodsA total of 397 consecutive HCC patients with curative‐intent hepatectomy were included. OSM‐positive cells and inflammatory cells including CD4‐, CD8‐, CD163‐, and FOXP3‐positive cells were immunohistochemically evaluated. We compared VETC‐positive and VETC‐negative HCCs in terms of the number of these cells.ResultsWe found the VETC pattern in 62 patients (15.6%). Our analysis revealed a significant decrease in the expression of arginase‐1, a marker associated with mature hepatocyte differentiation, in VETC‐positive HCC (p = 0.046). The number of tumor‐infiltrating OSM‐positive cells was significantly low in VETC‐positive HCC (p = 0.0057). Notably, in VETC‐positive HCC, the number of OSM‐positive cells was not associated with vascular invasion, whereas in VETC‐negative HCC, an increase in the number of OSM‐positive cells was associated with vascular invasion (p = 0.042).ConclusionsWe identified an association between a decrease in OSM‐positive cells and the VETC pattern. Additionally, our findings indicate that VETC‐positive HCC is characterized by low hepatocyte differentiation and OSM‐independent vascular invasion. These findings highlight the potential interaction between VETC‐positive HCC cells and their TIM through the reduction of OSM‐expressing cells.
Funder
Japan Society for the Promotion of Science
Subject
Infectious Diseases,Hepatology