Tumor budding has been reported to be an independent prognostic factor in pancreatic ductal adenocarcinoma (PDAC). Its use in daily diagnostics would improve the prognostic stratification of patients. We performed a multicenter interobserver study to test various budding assessment methods for their reproducibility. Two serial sections of 50 resected, treatment-naïve PDACs were stained for Hematoxylin and Eosin (H&E) and pancytokeratin. Tumor budding was scored by independent observers at five participating centers in Switzerland, Germany, and Canada. Pathologists assessed tumor budding on a digital platform comparing H&E with pancytokeratin staining in 10 high-power fields (10HPF) and one HPF hotspot (1HPF). Additionally, tumor budding was assessed in one H&E hotspot at × 20 magnification, as suggested by the International Tumor Budding Consensus Conference (ITBCC). Correlation coefficients for bud counts between centers ranged from r = 0.58648 to r = 0.78641 for H&E and from r = 0.69288 to r = 0.81764 for pancytokeratin. The highest interobserver agreement across all centers was observed for pancytokeratin 10HPFs (ICC = 0.6). ICC values were 0.49, 0.48, 0.41, and 0.4 for H&E in 1HPF hotspot, H&E in 10HPFs, pancytokeratin in 1HPF, and H&E in one hotspot at ×20, respectively (ITBCC method). This interobserver study reveals a range between moderately poor to moderate agreement levels between pathologists for the different tumor budding assessment methods in PDAC. Acceptable levels of agreement were reached with the pancytokeratin 10HPF method, which can thus be recommended for the assessment of tumor budding in PDAC resection specimens. To improve the levels of interobserver agreement, the implementation of machine learning applications should be considered.

据报道，肿瘤萌发是胰腺导管腺癌（PDAC）的独立预后因素。它在日常诊断中的使用将改善患者的预后分层。我们进行了一项多中心观察员研究，以测试各种萌芽评估方法的可重复性。对50例未治疗的PDAC的两个连续切片进行苏木精和曙红（H＆E）和全细胞角蛋白染色。在瑞士，德国和加拿大的五个参与中心，独立观察员对肿瘤萌芽进行了评分。病理学家在10个高倍视野（10HPF）和1个HPF热点（1HPF）中比较了H＆E和全角蛋白染色在数字平台上评估的肿瘤发芽。此外，在一个H＆E热点中以×20放大倍数评估了肿瘤出芽，根据国际肿瘤萌芽共识会议（ITBCC）的建议。中心之间芽数的相关系数范围为[R = 0.58648至- [R = 0.78641用于H＆E和从- [R = 0.69288至ř对于全细胞角蛋白＝ 0.81764。观察到所有中心的全细胞角蛋白10HPF观察者之间的一致性最高（ICC = 0.6）。在1HPF热点处的H＆E，10HPFs中的H＆E，10HPF中的H＆E，1HPF中的全细胞角蛋白和在20时一个热点中的H＆E的ICC值分别为0.49、0.48、0.41和0.4（ITBCC方法）。这项观察者间研究揭示了病理学家之间针对PDAC中不同肿瘤萌发评估方法的一致程度介于中等至中等之间。全细胞角蛋白10HPF方法达到了可接受的一致性水平，因此可以推荐用于评估PDAC切除标本中的肿瘤萌芽。为了提高观察者间协议的水平，应考虑机器学习应用程序的实现。