Contrast-enhanced intraoperative ultrasonography for vascular imaging of hepatocellular carcinoma: clinical and biological significance.

Unlabelled: Abnormal tumor vascularity is one of the typical features of hepatocellular carcinoma (HCC). In this study, the significance of contrast-enhanced intraoperative ultrasonography (CEIOUS) images of HCC vasculature was evaluated by clinicopathological and gene expression analyses. We enrolled 82 patients who underwent curative hepatic resection for HCC with CEIOUS. Clinicopathological and gene expression analyses were performed according to CEIOUS vasculature patterns. CEIOUS images of HCC vasculatures were classified as reticular HCC or thunderbolt HCC. Thunderbolt HCC was significantly correlated with higher alpha-fetoprotein levels, tumor size, histological differentiation, portal vein invasion, and tumor-node-metastasis stage, and these patients demonstrated a significantly poorer prognosis for both recurrence-free survival (P = 0.0193) and overall survival (P = 0.0362) compared with patients who had reticular HCC. Gene expression analysis revealed that a rereplication inhibitor geminin was significantly overexpressed in thunderbolt HCCs (P = 0.00326). In vitro knockdown of geminin gene reduced significantly the proliferation of human HCC cells. Immunohistochemical analysis confirmed overexpression of geminin protein in thunderbolt HCC (P < 0.0001). Multivariate analysis revealed geminin expression to be an independent factor in predicting poor survival in HCC patients (P = 0.0170).

Conclusion: CEIOUS vascular patterns were distinctly identifiable by gene expression profiling associated with cellular proliferation of HCC and were significantly related to HCC progression and poor prognosis. These findings might be clinically useful as a determinant factor in the postoperative treatment of HCC.