Tumour budding in pancreatic cancer revisited: validation of the ITBCC scoring system.

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy with rising incidence. Biomarkers that would help the prognostic stratification of patients are needed urgently. Although tumour budding (BD) is a strong and independent prognostic factor in PDAC it is not included in histopathology reports, due partly to the lack of a standardised scoring system. The aim of the present work is to assess the reliability and reproducibility of the BD scoring system proposed recently by the International Tumour Budding Consensus Conference (ITBCC) 2016 in a well-characterised PDAC cohort (n=120) with complete clinicopathological and follow-up information. BD was scored independently by two pathologists on haematoxylin and eosin-stained PDAC sections by assessing the densest budding area at ×20 magnification (one hot-spot, 0.785mm2 ), regardless of intra- or peritumoural localisation, and assigned to four categories: BD0: no buds; BD1: one to four buds; BD2: five to nine buds; and BD3: ≥10 buds. Findings were correlated to patient and tumour characteristics and interobserver agreement was assessed. The weighted kappa value for BD category was 0.62 (0.5-0.73), indicating strong agreement. Increasing BD category (BD3 versus BD0-2) correlated with higher grade (P=0.002) and shorter overall [OS, P<0.0001, hazard ratio (HR)=3.234, 95% confidence interval (CI)=1.95-5.37] and disease-free survival (DFS, P=0.0135, HR=1.974, 95% CI=1.15-3.39). BD (BD3 versus BD0-2) was an independent prognostic factor for OS and DFS, after adjusting for tumour-node-metastasis (TNM) stage by using both the 8th American Joint Committee on Cancer (AJCC) edition (OS: P=0.0031, HR= 2.298, 95% CI=1.32-0.99; DFS: P=0.0458, HR=1.713, 95% CI=1.01-2.91) and the 7th AJCC edition (OS: P<0.0001, HR=2.795,95% CI=1.71-4.57 and DFS: P=0.00786, HR=1.643, 95% CI=0.95-2.86). ITBCC scoring is a simple, reliable and reproducible method to evaluate BD in PDAC and facilitates its documentation in histopathology reports, allowing the prognostic stratification of PDAC patients.