Intensity of Tumor Budding and Its Prognostic Implications in Invasive Colon Carcinoma

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Abstract
The aim of this study was to assess the intensity of tumor budding in colon carcinoma quantitatively and to determine its correlation with malignancy potential. The intensities of tumor budding at the invasive front of surgical specimens from 174 patients with well-differentiated or moderately differentiated colon carcinoma were investigated. Differences in intensity among clinicopathologic parameters were compared, and recurrences and survivals were analyzed in accordance with degree of the intensity. Tumor budding was identified in 155 patients (89 percent) and the mean intensity (± standard deviation) of budding was, on the whole, 6.6 ± 5.6. Intensity was significantly higher in tumors with lymphatic and vascular invasion than in those without (9.1 ± 6.6vs. 4.8 ± 3.9 and 9.8 ± 6.1vs. 5.4 ± 4.9;P< 0.0001, respectively). It became significantly higher with increasing T and N stage (P= 0.0013 and < 0.0001, respectively). Both the Cox model and the linear logistic regression indicated that higher intensity was significantly associated with higher risk of postoperative recurrence (P= 0.017 and 0.0001, respectively). When patients were stratified into four groups based on the quartiles of the distribution of intensity, the group of higher quartiles showed significantly less favorable outcome in terms of both five-year disease-free (P= 0.0039) and overall survival (P= 0.0263). The cutoff of the intensity considered to be the best indicator for separating patients with regard to survival was third quartiles (intensity, 9). Based on multivariate analysis, the intensity of budding proved to be a significant covariate associated with disease-free survival (hazard ratio, 2.061;P= 0.0066). The intensity of tumor budding at the invasive margin is suggested to be a significant pathologic index, indicating higher malignancy potential and the intensity greater than nine may be considered an adverse prognostic indicator in patients with colon carcinoma.