Tumour Budding in Pancreatic Cancer revisited: Validation of the ITBCC Scoring System

Abstract

Background

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy with rising incidence. Biomarkers that would help the prognostic stratification of patients are urgently needed. Although tumour budding (BD) is a strong and independent prognostic factor in PDAC, is not included in histopathology reports, partly due to lack of standardized scoring system.

Aim

Aim of the present work is to assess the reliability and reproducibility of the BD scoring system recently proposed by the International Tumour Budding Concensus Conference (ITBCC) 2016, in a well-characterized PDAC-cohort (n=120) with complete clinico-pathological and follow-up information.

Methods

BD was scored independently by two pathologists on H&E-stained PDAC-sections by assessing the densest budding area at 20x-magnification (one "hotspot", 0.785mm²) regardless of intra-or peritumoural localisation and assigned into four categories: BD0: 0 buds; BD1: 1-4 buds; BD2: 5-9 buds; and BD3: ≥10 buds. Findings were correlated to patient and tumour characteristics und inter-observer agreement was assessed.

Results

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; HR(95%CI)=3.234(1.95-5.37)) and disease-free survival (DFS, p=0.0135; HR(95%CI)=1.974(1.15-3.39)). BD (BD3 versus BD0-2) was an independent prognostic factor for OS and DFS, after adjusting for TNM-stage by using both the 8^th AJCC Edition (OS; p=0.0031;HR(95%CI)=2.298(1.32-.99)); (DFS; p=0.0458;HR(95%CI)=1.713(1.01-2.91)) and the 7^th AJCC Edition (OS; p<0.0001;HR(95%CI)=2.795(1.71-4.57)) and (DFS; p=0.00786;HR(95%CI)=1.643(0.95-2.86)).

Conclusions

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.

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