Fig. 2

Definition and detection of tumor buds. a Example single TMA core stained for pan-cytokeratin and hematoxylin and eosin (HE). The red circle highlights a tumor bud next to larger tumor island. The blue circle is a small tumor part, which we referred to as a “tumor islet”; which is a small tumor aggregate but does not meet all criteria for a tumor bud. b Histogram of pan-cytokeratin positive tumor area per core (upper plot) and pan-cytokeratin tumor bud area per core (lower plot). One can see that the mean area of all tumor fragments (upper panel) shows a huge dispersion (x-axis 0–100,000), whereas the mean area of the tumor buds is less distributed (x-axis 0–1000)