Tumor budding as a prognostic marker in stage-III rectal carcinoma

Background and aims Tumor budding along the invasive margin is known to be associated with biological behavior in colorectal carcinoma. The aims of this study were to explore if the semiquantitative assessment of tumor budding in rectal cancers correlates with oncological behavior and to appraise if the tumor budding is valid as a pathological parameter in distinguishing tumors with higher malignancy potential from those with lower one for prognostic stratification. Materials and methods Surgical specimens from 244 patients with well- or moderately differentiated rectal carcinoma were retrieved to assess the intensity of tumor budding at the invasive margin. Intensities were divided semiquantitatively into four groups based on quartiles, and the 5-year disease-free survivals (DFS) were analyzed to search for a cutoff point of prognostic stratification. Results The cutoff of the intensity considered to be the best indicator for dividing patients into subgroups with different DFS was between quartiles 3 and 4, but this survival difference in subgroups in either side of the cutoff was significant only in stage-III disease [5-year DFS, 62.1 vs 35.1%; p=0.0023; 95% confidence interval (CI), 0.1824-0.6919]. Based on multivariate analysis, the intensity of budding proved to be an independent variable associated with DFS (hazard ratio, 2.005; p=0.0086; 95% CI, 1.021-3.934). When scores were given to grade of budding (lower, 0; higher, 1) and N stage (N1, 0; N2, 1) in stage III, a better prognostic stratification in terms of the 5-year DFS was obtained than the American Joint Committee on Cancer nodal staging only (0 vs 1 vs 2, 66.5 vs 42.6 vs 29.2%; p=0.0101). Conclusions Quantitative assessment of tumor budding is a reliable biological prognostic variable to identify higher malignancy potential. Scoring system using tumor budding and N stage showed better prognostic stratification in stage-III rectal carcinoma. A prospective evaluation would confirm the clinical significance of tumor budding for prognostic stratification.