title: Tumor budding is an independent adverse prognostic factor in pancreatic ductal adenocarcinoma.
abstract: Tumor budding is a well-established adverse prognostic factor in colorectal cancer. However, the significance and diagnostic reproducibility of budding in pancreatic carcinoma requires further study. We aimed to assess the prognostic significance of tumor budding in pancreatic ductal adenocarcinoma, determine its relationship with other clinicopathologic features, and assess interobserver variability in its diagnosis. Tumor budding was assessed in 192 archival cases of pancreatic ductal adenocarcinoma using hematoxylin and eosin (H&E) sections; tumor buds were defined as single cells or nonglandular clusters composed of <5 cells. The presence of budding was determined through assessment of all tumor-containing slides, and associations with clinicopathologic features and outcomes were analyzed. Six gastrointestinal pathologists participated in an interobserver variability study of 120 images of consecutive tumor slides stained with H&E and cytokeratin. Budding was present in 168 of 192 cases and was associated with decreased overall survival (P=0.001). On multivariable analysis, tumor budding was prognostically significantly independent of stage, grade, tumor size, nodal status, lymphovascular invasion, and perineural invasion. There was substantial agreement among pathologists in assessing the presence of tumor budding using both H&E (K=0.63) and cytokeratin (K=0.63) stains. The presence of tumor budding is an independent adverse prognostic factor in pancreatic ductal carcinoma. The assessment of budding with H&E is reliable and could be used to better risk stratify patients with pancreatic ductal adenocarcinoma.
authors: Divisions of *Anatomic Pathology #General Surgery, Vancouver General Hospital †The University of British Columbia ‡Pancreas Centre BC §Division of Medical Oncology, BC Cancer Agency, Vancouver, BC ∥Department of Pathology, Western University, London ¶Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
authors: Kate
authors: K
authors: O'Connor
authors: Hector H
authors: HH
authors: Li-Chang
authors: Steven E
authors: SE
authors: Kalloger
authors: Renata D
authors: RD
authors: Peixoto
authors: Douglas L
authors: DL
authors: Webber
authors: David A
authors: DA
authors: Owen
authors: David K
authors: DK
authors: Driman
authors: Richard
authors: R
authors: Kirsch
authors: Stefano
authors: S
authors: Serra
authors: Charles H
authors: CH
authors: Scudamore
authors: Daniel J
authors: DJ
authors: Renouf
authors: David F
authors: DF
authors: Schaeffer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D001706:Biopsy; D021441:Carcinoma, Pancreatic Ductal / Q000737:chemistry / Q000401:mortality / Q000473:pathology*; D016009:Chi-Square Distribution; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D015588:Observer Variation; D010190:Pancreatic Neoplasms / Q000737:chemistry / Q000401:mortality / Q000473:pathology*; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D015203:Reproducibility of Results; D012189:Retrospective Studies; D012307:Risk Factors; D013194:Staining and Labeling / Q000379:methods; D013997:Time Factors
chemical_list: D014408:Biomarkers, Tumor