Tumor Budding in Gastric Carcinoma: Beyond Counting Cells at the Invasive Front-A Review of Current Evidence and Biological Perspectives.

Tumor budding is increasingly recognized as a histopathologic feature associated with invasive behavior in gastrointestinal malignancies. While its prognostic value is well established in colorectal carcinoma, its significance in gastric adenocarcinoma remains less clearly defined because of marked morphologic heterogeneity, variable growth patterns, and the absence of gastric-specific assessment criteria. Multiple studies have associated high budding density with adverse clinicopathologic features, including lymph node metastasis, lymphovascular invasion, advanced tumor stage, and poorer survival, particularly in intestinal-type tumors. However, these associations are more difficult to interpret in diffuse-type and mixed carcinomas, where intrinsic discohesion and architectural variability complicate the distinction between true budding and baseline growth patterns. Beyond prognostic assessment, tumor budding has been linked to localized alterations in cell adhesion, cytoskeletal organization, tumor-stroma interaction, and partial epithelial-mesenchymal transition. Emerging evidence also suggests that its biological significance may differ across molecular subtypes of gastric cancer. This review examines the current evidence on the definition, morphologic spectrum, methodological limitations, and biologic context of tumor budding in gastric adenocarcinoma. We propose that, in gastric cancer, tumor budding is best interpreted not as a uniformly applicable scoring parameter, but as a context-dependent morphologic indicator of invasive tumor remodeling whose meaning varies according to tumor architecture, stromal interface, and molecular subtype.