Evaluating tumour budding could improve the new grading system for lung adenocarcinoma

Objectives: To study the prognostic significance of tumour budding (TB) compared with the grading of lung adenocarcinoma (LAC). Materials and methods: The postoperative haematoxylin and eosin-stained histological slices of 207 surgically treated LAC patients were retrospectively reviewed by a lung pathologist. Two groups were formed from the cohort: the high-grade TB group (≥10 buds) and low-grade TB group (0–9 buds). The prognostic significance of high-grade TB for the 5-year progression-free survival (PFS) and overall survival (OS) of patients was studied using the Kaplan–Meier method and Cox regression models. A novel four-tier grading system for LACs was developed by combining the World Health Organization (WHO) grading system and high-grade TB. The computed tomography (CT) imaging features of the tumours were assessed semiquantitatively by two chest radiologists. Results: There were 166 patients with low-grade TB and 41 LAC patients with high-grade TB. Most of the tumours with high-grade TB were Grade 3 tumours. The median follow-up time was 60 months. The 5-year PFS was lower in the high-grade TB group than in the low-grade TB group (37.6 vs. 50.9 months, p < 0.001). High-grade TB remained an independent prognostic factor for poor PFS (clinical model: hazard ratio [HR] = 2.07, adj. p = 0.012, histopathological model: adj. HR = 2.09, adj. p = 0.010). Compared with the WHO Grade 3 group, the Novel Grade 4 group had a shorter mean PFS (36.7 vs. 45.3 months), and according to the PFS analysis, the novel four-tier grading system was superior to the WHO grading system (AIC = 591.9 vs. AIC = 596.6, ΔAIC > 2). On CT, tumours with higher TBs are usually smooth or spiculated. Conclusion: This is the first study to show that high-grade TB is associated with a higher LAC grade. The incorporation of TB into the WHO grading scheme may improve the prognostic significance of LAC grading.