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Tumor budding is a meaningful prognostic marker in patients with hepatocellular carcinoma after curative hepatectomy

Kaibo Yang,Kunjin Wu,Zitong Lei,Tong Liu,Xing Zhang,Jing Li,Kun Yang,Qiuting Peng,Ting Lin,Chang Liu,Kai Qu

Aim Tumor budding (TB) has excellent prognostic value in many solid tumors, but there is little research on it in hepatocellular carcinoma (HCC). This study assessed the prognostic value of TB in patients with HCC who received hepatectomy. Methods This retrospective study included 210 patients with HCC who received curative hepatectomy at the First Affiliated Hospital of Xi'an Jiaotong University, between 2016 and 2018. TB was evaluated on hematoxylin- and eosin-stained slides according to the criteria established by the 2016 International Tumor Budding Consensus Conference. t -tests, Chi-squared tests, and rank-sum tests were used to correlate the extent of TB with clinicopathological parameters. Prognostic analysis was performed using Cox regression models and the Kaplan–Meier method. Results The positive detection rate of TB was 45.2% (95/210) in 210 patients with HCC. Patients positive for TB always exhibit lower tumor differentiation, higher hepatitis B virus DNA levels, and more severe liver fibrosis. Multivariate Cox analysis identified TB (hazard ratio [HR]: 2.232, 95% confidence interval [CI]: 1.479–3.368, p < 0.001) as an independent prognostic factor for patients' recurrence-free survival (RFS), similar to tumor size (HR: 1.070, 95% CI: 1.070–1.142, p = 0.042) and satellite nodule (HR: 2.266, 95% CI: 1.298–3.956, p = 0.004). Kaplan–Meier analysis also demonstrated that TB-positive patients had a significantly worse RFS. Interestingly, subgroup analysis revealed that among HCC patients with negative microvascular invasion (MVI), TB was also strongly associated with RFS (HR: 3.206, 95% CI: 1.667–6.168, p < 0.001). These findings suggest that TB may serve as a supplemental prognostic biomarker for HCC-negative MVI. Conclusions TB is an adverse prognostic biomarker for HCC, particularly in patients negative for MVI. TB evaluation should be considered in the postoperative pathological examination of HCC in clinical practice. Graphical This study assessed tumor budding (TB) in hepatocellular carcinoma patients. TB refers to the detachment of tumor cells from the primary tumor mass, infiltrating the adjacent matrix and forming separate clusters. It may represent two distinct pathological features compared to microvascular invasion, which involves the invasion of tumor cells into microvessels. ECM: extracellular matrix. Key points Significant findings of the study This single-center study found that tumor budding (TB) positivity was significantly associated with poor prognosis in patients with hepatocellular carcinoma (HCC). What this study adds TB could serve as a potential supplemental prognostic biomarker for HCC with negative microvascular invasion.