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

To study the prognostic significance of tumour budding (TB) compared with the grading of lung adenocarcinoma (LAC).

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.

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.

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.