Abstract
The basis of personalized medicine in oncology is the prediction of an individual’s risk of relapse and death from disease. The presence of tumor budding (TB) at the tumor–host interface of gastrointestinal cancers has been recognized as a hallmark of unfavorable disease biology. TB is defined as the presence of dedifferentiated cells or small clusters of up to five cells at the tumor invasive front and can be observed in aggressive carcinomas of the esophagus, stomach, pancreas, ampulla, colon, and rectum. Presence of TB reproducibly correlates with advanced tumor stage, frequent lymphovascular invasion, nodal, and distant metastasis. The UICC has officially recognized TB as additional independent prognostic factor in cancers of the colon and rectum. Recent studies have also characterized TB as a promising prognostic indicator for clinical management of esophageal squamous cell carcinoma, adenocarcinoma of the gastro-esophageal junction, and gastric adenocarcinoma. However, several important issues have to be addressed for application in daily diagnostic practice: (1) validation of prognostic scoring systems for TB in large, multi-center studies, (2) consensus on the optimal assessment method, and (3) inter-observer reproducibility. This review provides a comprehensive analysis of TB in cancers of the upper gastrointestinal tract including critical appraisal of perspectives for further study.
Highlights
The foundation of personalized oncological therapy is the prediction of an individual’s risk of relapse and death from disease
Tumor budding is frequently observed in carcinomas of the upper gastrointestinal tract
Information on tumor budding (TB) provided by the histopathologist could be of particular value for personalized patient management in two distinct clinical scenarios: first, information on TB could be an important factor for risk stratification of patients with locally invasive squamous cell carcinoma (SCC) or AC of the esophagus (15, 19)
Summary
The foundation of personalized oncological therapy is the prediction of an individual’s risk of relapse and death from disease. In cancers of the upper gastrointestinal tract, we know that unexpected adverse clinical outcomes can be observed in patients even with early-stage disease (4, 5). Exhibit a low proliferative activity, which is in line with their migratory phenotype (38, 40) Taken together, these features may explain an increased resistance of tumor buds to chemo- and radiotherapy. Few studies have investigated the immunogenicity of tumor buds, but it has been suggested that loss of MHC-I expression could be a frequent feature in cancer initiating cells (42). Tumor buds may possess stem cell like features, as suggested by an increased expression of ABCG-5 protein (44). These stem cell characteristics may allow cancer initiation at distant sites (Figure 2). Subject of this review is to provide a comprehensive overview on Frontiers in Oncology | Gastrointestinal Cancers
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