Immunological and prognostic significance of vessels encapsulating tumor clusters (VETC) in hepatocellular carcinoma.

Background: Vessels encapsulating tumor clusters (VETC) has been identified as a poor prognostic indicator in hepatocellular carcinoma (HCC). However, the detailed tumor microenvironment in VETC-positive HCC remains unclear. We investigated the prognostic significance of VETC and elucidated the immune cell profile of VETC-positive HCC.

Methods: We enrolled 229 patients who underwent hepatic resection for HCC. We performed immunohistochemistry for CD34, CD8 and CD163, combined with digital image analysis, on resected specimens to evaluate their immune profile in both the tumor center and invasive margin. The relationships between VETC and clinicopathological features, including immune cell densities were investigated.

Results: A total of 78 patients (34 %) had VETC-positive HCC. Univariate and multivariate analyses revealed that VETC was significantly associated with poor disease-free (p = 0.001 and p = 0.023) and overall survival (p = 0.001 and p = 0.032). VETC-positive HCC exhibited higher serum PIVKA-II levels (217 mAU/ml vs. 40 mAU/ml, p = 0.001), moderate/poor differentiation (92 % vs. 75 %, p = 0.002), larger tumor size (4.8 cm vs. 3.0 cm, p < 0.001), and microvascular invasion (32 % vs. 11 %, p < 0.001). The densities of CD8 cells and CD163 cells in the tumor center were significantly lower in VETC-positive HCC compared with those in VETC-negative HCC (p < 0.001 and p = 0.024, respectively). A similar trend was observed in densities of CD8 cells and CD163 cells in the invasive margin (p = 0.061 and p = 0.064, respectively).

Conclusion: VETC may regulate immune cell infiltration into tumors, especially in the tumor center, and serves as a poor prognostic indicator in HCC.