# Pathological and Clinical Significance of Tumor Budding and Its Association with Epithelial-Mesenchymal Transition in Colorectal Carcinoma: A Retrospective Observational Study

## TL;DR

This study explores how tumor budding in colorectal cancer relates to cancer spread and markers of cell transition.

## Contribution

The study provides new insights into tumor budding's clinical significance and its relationship with epithelial-mesenchymal transition markers in colorectal cancer.

## Key findings

- Tumor budding is significantly linked to advanced tumor stage, invasion, and metastasis in colorectal cancer.
- Aberrant expression of EMT markers like β-catenin and ZEB1 is common but not significantly associated with tumor budding.
- Lymph node metastasis occurs in 93% of cases with tumor budding.

## Abstract

Metastases, not the primary tumor, account for most cancer-related deaths. Tumor budding, thought to represent epithelial-mesenchymal transition (EMT), has garnered attention due to its association with invasion and migration. This study aims to assess the pathological and clinical significance of tumor budding in colorectal carcinoma and its correlation with epithelial-mesenchymal transition.

In this retrospective observational study, tissue samples from 101 patients (no neoadjuvant treatment) were analyzed. Tumor budding was scored using International Tumor Budding Consensus Conference guidelines and classified into Budding 1 (BD1) (1-4 buds), Budding 2 (BD2) (5-9 buds), and Budding 3 (BD3) (10+ buds) per 0.785 mm². The tissue sample was subjected to immunohistochemistry to assess EMT markers β-catenin, E-cadherin, Snail, and Zinc finger E-box-binding homeobox 1 (ZEB1).

Tumor budding was significantly associated with advanced tumor stage (P=0.0001), deeper invasion (P=0.003), vascular invasion (P=0.001), perineural invasion (P=0.0001), and desmoplasia (P=0.010). Regional lymph node metastasis was seen in 93% of cases with tumor budding, and distant metastasis was found in eight cases (7.9%). Aberrant β-catenin expression was seen in 82 cases (81.2%), and aberrant E-cadherin in 65 cases (64.4%). Snail and ZEB1 positivity were observed in 55 (54.5%) and 32 (31.7%) cases, respectively. A significant correlation was found between aberrant β-catenin and ZEB1 (P=0.005). Although EMT markers coexisted frequently with tumor budding, no statistically significant association was observed.

The results of our study indicate that tumor budding is common in colorectal carcinoma and is significantly associated with advanced tumor stage, invasion, vascular and perineural invasion, and regional lymph node metastasis. Aberrant expression of EMT markers (β-catenin, E-cadherin, Snail, and ZEB1) was frequently observed, although no significant association with tumor budding was found.