Tumor budding as a potential histopathological biomarker in colorectal cancer: hype or hope?

Colorectal cancer (CRC), the third most commonly diagnosed type of cancer in men and women worldwide is recognized as a complex multi-pathway disease, an observation sustained by the fact that histologically identical tumors may have different outcome, including various response to therapy. Therefore, particularly in early and intermediate stage (stages II and III, respectively) CRC, there is a compelling need for biomarkers helpful of selecting patients with aggressive disease that might benefit from adjuvant and targeted therapy. Histopathological examination shows that likely other solid tumors the development and progression of human CRC is not only determined by genetically abnormal cells, but also by intricate interactions between malignant cells and the surrounding microenvironment. This has led to reconsider the features of tumor microenvironment as potential predictive and prognostic biomarkers. Among the histopathological biomarkers, tumor budding (i.e., the presence of individual cells and small clusters of tumor cells at the tumor invasive front) has received much recent attention, particularly in the setting of CRC. Although its acceptance as a reportable factor has been held back by a lack of uniformity with respect to qualitative and quantitative aspects, tumor budding is now considered as an independent adverse prognostic factor in CRC that may allow for stratification of patients into risk categories more meaningful than those defined by tumor-node-metastasis staging alone, and also potentially guide treatment decisions, especially in T2-T3 N0 (stage II) CRCs.