Tumor Budding in Colorectal Cancer: Biological Basis, Clinical Risk Stratification, and Digital Pathology
4 affiliations
- 1Department of Internal Medicine, Hospital General Universitario Reina Sofía, 30003 Murcia, Spain
- 2Department of Medicine, Faculty of Medicine, University of Murcia, 30120 El Palmar, Spain
- 3Department of Pathology, Hospital General Universitario Reina Sofía, 30003 Murcia, Spain
- 4Department of Ophthalmology, Optometry, Otolaryngology and Pathology, Faculty of Medicine, University of Murcia, 30120 El Palmar, Spain
Abstract
Tumor budding, defined as single tumor cells or clusters of up to four cells at the invasive front, is a morphological marker of tumor-cell dissociation and stromal invasion in colorectal cancer. Standardization by the International Tumor Budding Consensus Conference (ITBCC) established a reproducible hematoxylin-and-eosin-based method and enabled broader incorporation of budding into pathology reporting and clinical risk assessment. Intermediate- and high-grade budding are associated with lymph node metastasis in pT1 colorectal cancer, while high-grade budding identifies a subgroup of stage II colon cancers with increased recurrence risk. Adverse prognostic associations have also been reported in stage III disease and in rectal cancer after neoadjuvant therapy, although evidence that budding predicts benefit from a specific treatment is still insufficient. At the biological level, budding is linked to partial epithelial–mesenchymal transition, altered cell adhesion, cytoskeletal remodeling, and interactions with fibroblasts, extracellular matrix, and immune cells. Digital pathology and artificial intelligence may improve hotspot selection, quantification, and spatial characterization, but their clinical use depends on external validation, control of domain shift, and continued pathologist oversight. Tumor budding is therefore best interpreted as a complementary morphological biomarker alongside TNM stage, established histopathological risk factors, molecular features, and clinical context.
Related
- A Histology‐Derived Score Integrating Tumor–Stroma Ratio, Tertiary Lymphoid Structures, and Tumor Budding Improves Prognostic Stratification in Colorectal Cancer
- The molecular pathological basis and potential clinical applications of ‘zero‐budding’ status in stage II colorectal cancer
- Toward Precision Colorectal Cancer Screening: Integrating Clinical Risk Stratification, Molecular Biomarkers, and Artificial Intelligence
- Prognostic significance of tumor budding and poorly differentiated clusters in colorectal cancer : A retrospective study
- The prognostic value of tumour budding for survival in stage II and III colorectal cancer: a systematic review and meta‐analysis
BibTeX
@article{bernalmorell2026tumor,
title = {{Tumor Budding in Colorectal Cancer: Biological Basis, Clinical Risk Stratification, and Digital Pathology}},
author = {Enrique Bernal-Morell and Francisco Martínez-Díaz and Francisco García-Molina},
journal = {Cancers},
year = {2026},
month = oct,
doi = {10.3390/cancers18213493},
url = {https://www.mdpi.com/2072-6694/18/21/3493},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Tumor Budding in Colorectal Cancer: Biological Basis, Clinical Risk Stratification, and Digital Pathology
AU - Enrique Bernal-Morell
AU - Francisco Martínez-Díaz
AU - Francisco García-Molina
PY - 2026
DA - 2026/10/29
JO - Cancers
DO - 10.3390/cancers18213493
UR - https://www.mdpi.com/2072-6694/18/21/3493
AB - Tumor budding, defined as single tumor cells or clusters of up to four cells at the invasive front, is a morphological marker of tumor-cell dissociation and stromal invasion in colorectal cancer. Standardization by the International Tumor Budding Consensus Conference (ITBCC) established a reproducible hematoxylin-and-eosin-based method and enabled broader incorporation of budding into pathology reporting and clinical risk assessment. Intermediate- and high-grade budding are associated with lymph node metastasis in pT1 colorectal cancer, while high-grade budding identifies a subgroup of stage II colon cancers with increased recurrence risk. Adverse prognostic associations have also been reported in stage III disease and in rectal cancer after neoadjuvant therapy, although evidence that budding predicts benefit from a specific treatment is still insufficient. At the biological level, budding is linked to partial epithelial–mesenchymal transition, altered cell adhesion, cytoskeletal remodeling, and interactions with fibroblasts, extracellular matrix, and immune cells. Digital pathology and artificial intelligence may improve hotspot selection, quantification, and spatial characterization, but their clinical use depends on external validation, control of domain shift, and continued pathologist oversight. Tumor budding is therefore best interpreted as a complementary morphological biomarker alongside TNM stage, established histopathological risk factors, molecular features, and clinical context.
SN - 2072-6694
ER -