To investigate the relation between tumor budding in pathological specimens of patients with hepatocellular carcinoma and clinicopathological characteristics, and its impact on the recurrence after hepatectomy.

A retrospective analysis was performed on the clinicopathological data of 107 patients who underwent hepatectomy for hepatocellular carcinoma in Southe Hospital to Xiamen University from January 2020 to December 2021. There were 58 males and 49 females; the age was (60±6) years. The informed consents of all patients were obtained and the local ethical committee approval was received. Based on postoperative pathological findings, the relation between tumor budding in cancer tissue and clinicopathological characteristics was analyzed. According to whether tumor recurrence occurred, patients were divided into a recurrence group (n=39) and a non-recurrence group (n=68). The correlation between tumor budding and clinicopathological characteristics was analyzed using the χ² test. Cox univariate and multivariate analyses were used to identify factors associated with recurrence of hepatocellular carcinoma. Recurrence-free survival was analyzed using the Kaplan-Meier method and the Log-rank test.

Compared with low-grade tumor budding, patients with high-grade tumor budding had higher proportions of maximum tumor diameter ≥ 5 cm, multiple tumors, microvascular invasion (MVI), incomplete capsule, moderate-to-poor differentiation, venous invasion, and TNM stage Ⅲ-Ⅳ (χ²=7.666, 9.805, 12.022, 6.847, 4.142, 6.538, 4.503; P < 0.05). Cox univariate analysis showed that multiple tumors (HR=3.155, 95%CI: 1.074-9.267), MVI (HR=2.791, 95%CI: 1.516-5.048), incomplete capsule (HR=4.903, 95%CI: 1.266-5.984), high-grade tumor budding (HR=6.406, 95%CI: 1.349-8.071), and TNM stage Ⅲ-Ⅳ (HR=4.102, 95%CI: 1.698-5.807) were associated with postoperative recurrence (P < 0.05). Cox multivariate regression analysis indicated that multiple tumors (HR=3.342, 95%CI: 1.840-5.049), MVI (HR=5.722, 95%CI: 1.928-7.387), incomplete capsule (HR=3.693, 95%CI: 1.492-6.427), high-grade tumor budding (HR=4.556, 95%CI: 1.912-7.908), and TNM stageⅢ-Ⅳ (HR=4.470, 95%CI: 1.846-7.631) were risk factors for postoperative recurrence of hepatocellular carcinoma (P < 0.05). The follow-up duration ranged from 9 to 57 months, with a median follow-up of 39 months. Survival analysis showed that the cumulative recurrence rates at 1, 3, and 5 years after surgery were 8.53%, 78.65%, and 86.71% in the high-grade tumor budding group, and 0, 18.62%, and 31.36% in the low-grade group, with a statistically significant difference (χ²=14.039, P < 0.001).

In patients with hepatocellular carcinoma, high-grade tumor budding is correlated with adverse pathological features, including maximum tumor diameter ≥5 cm, multiple tumors, MVI, incomplete capsule, moderate-to-poor differentiation, venous invasion, and TNM stageⅢ-Ⅳ.High-grade tumor budding is an independent risk factor for postoperative recurrence, and patients with high-grade tumor budding have a higher postoperative recurrence rate and a poorer prognosis.