Tumor Budding as a Prognostic Marker in Primary Colon Cancer - A Single Center Experience.

Introduction: Tumor budding (TB) is considered to be a morphological and prognostic factor relevant to colon cancer (CC). The aim of our study is to assess the TB and to evaluate its relationship to clinicopathological findings within stage II and III CC patients as a single center experience. Materials and methods: A total of 120 CC patients operated between 2018 and 2021 at the University Clinic of Digestive Surgery in Skopje, the Republic of North Macedonia were included in this retrospective, single center study. TB was evaluated by the magnification of 200x along the invasive front of the primary tumor on H&E and CKAE1/AE3 immunohistochemically stained sections. Two grades were used: low grade (TB1, 0-4 TBs) and high-grade, which includes intermediate (TB2, 5-9 TBs) and high grade (TB3 ≥10TBs) of TBs. Results: A statistically significant correlation has been identified between high-grade TB and age (p=0.05) of the patients. There was also a significantly higher occurrence of high-grade TB in patients within stage III CC. Statistically significant correlations were also found in lymph node status (p<0.01), vascular invasion (p<0.05), lymphatic invasion (p<0.01), postoperative relapse (p<0.01), and death (p<0.01). Tumor relapse and death were significantly more frequent in patients with high-grade TB than those with low-grade TB. Patients with registered high-grade TB demonstrated significantly lower relapse-free survival (RFS) and overall survival (OS) rates than patients with low-grade TB over the observation period (RFS: 53.8% vs. 98.5%, p<0.001; OS: 65.4% vs. 97.1%, p<0.001, respectively). Patients with lung and liver postoperative relapses had higher percentage of cases with high-grade TB (94.1%). Conclusion: Our results are highly suggestive that TB should be included as a histological biomarker in the pathology report of patients with stage II and stage III CC, because of its prognostic value.