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Tumour budding in pancreatic cancer revisited: validation of the ITBCC scoring system
Author(s) -
Karamitopoulou Eva,
Wartenberg Martin,
Zlobec Inti,
Cibin Silvia,
Worni Mathias,
Gloor Beat,
Lugli Alessandro
Publication year - 2018
Publication title -
histopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.626
H-Index - 124
eISSN - 1365-2559
pISSN - 0309-0167
DOI - 10.1111/his.13508
Subject(s) - medicine , hazard ratio , confidence interval , pancreatic cancer , pancreatic ductal adenocarcinoma , histopathology , pathology , malignancy , cytopathology , oncology , gastroenterology , cancer , cytology
Aims 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. Methods and results 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, 0.785 mm 2 ), regardless of intra‐ or peritumoural localisation, and assigned to four categories: BD 0: no buds; BD 1: one to four buds; BD 2: five to nine buds; and BD 3: ≥ 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 ( BD 3 versus BD 0–2) 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 ( BD 3 versus BD 0–2) 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). 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.