Tumor Budding: A Prognostic Marker of Aggressiveness and Metastatic Potential in Epithelial Cancers, with a Focus on Colorectal and Urothelial Carcinomas

A hallmark of malignancy is the ability of a tumor to disseminate and metastasize, a process that requires specific cellular adaptations. The American Joint Committee on Cancer developed the TNM staging system to classify malignancies and guide treatment strategies, reflecting the biological behavior and clinical outcomes of cancers. Despite its usefulness, ongoing efforts aim to identify additional diagnostic and prognostic parameters to improve accuracy and treatment outcomes. One such parameter is tumor budding, a distinctive morphological feature observed in epithelial cancers. tumor budding is characterized by single tumor cells or small clusters of up to four cells that detach from the invasive front and invade the surrounding stroma. First described in colorectal cancer, tumor budding has since been widely investigated and recognized as a predictor of adverse outcomes, including lymph node invasion, local and distant metastasis, lymphovascular invasion, and poor survival rates across multiple cancer types. Independent of pathological stage, tumor budding correlates with aggressive tumor behavior, highlighting its prognostic significance. In urothelial cancers, tumor budding has been linked to stage progression, distant metastasis, and survival outcomes, particularly in non-muscle invasive bladder cancer and muscle-invasive bladder cancer. This review examines the mechanisms underlying tumor budding, its clinical significance across various tumor types, and its prognostic implications in epithelial cancers. Understanding these factors could provide valuable insights into integrating tumor budding into routine pathological assessments and improving cancer management strategies.