Tumour budding and tumour-stroma ratio in hepatocellular carcinoma

Tumour budding has been linked with poor prognosis in hepatocellular carcinoma (HCC), while the prognostic value of tumour-stroma ratio (TSR) remains unclear. We assessed the prognostic value of tumour buds and TSR in HCC.

506 HCC cases were included. Survival analysis was performed separately for surgical (n=101) and non-surgical patients (n=405) based on the presence of tumour buds, and having low TSR (<50 %) and high TSR (≥50 %). Bud-positive patients were further categorised according to tumour bud quantity (1-4 buds, 5-9 buds, and ≥10 buds), and the presence of tumour buds accross multiple sections of the same tumour was evaluated. We also analysed the correlation of tumour buds and TSR between biopsy and resection samples.

Positive tumour budding was not associated with increased 5-year overall mortality in multivariable analysis (HR 2.00, 95 % CI, 0.98-4.07), but was an independent risk factor for disease-specific mortality (HR 2.53, 95 % CI, 1.06-6.02, P = 0.036). The presence of ≥10 buds was an independent risk factor of overall- and disease-specific mortality in multivariable analysis. Tumour buds were found in 77% of slides in bud-positive patients. TSR was not linked with 5-year overall survival or disease-specific survival. Biopsy samples demonstrated a low sensitivity of 22 % in identifying tumour budding compared to the resection samples.

Tumour budding was an independent risk factor for disease-specific mortality in surgically treated HCC patients, with higher bud counts indicating poorer outcomes. Tumour buds were consistently found across slides. Furthermore, our results suggest that tumour buds are most reliably evaluated using resection samples.