Tumor Budding as an Index to Identify High-Risk Patients with Stage II Colon Cancer

Abstract

High-risk patients with Stage II colon cancer may benefit from adjuvant chemotherapy, but they are difficult to identify. We assessed the value of tumor budding, defined as small clusters of undifferentiated cancer cells at invasive margins, as a predictor of outcomes in patients with Stage II colon cancer. We studied a total of 200 patients with Stage II colon cancer who underwent curative surgery. With hematoxylin and eosin-stained specimens, the degree of tumor budding was classified as low-grade or high-grade. The survival rate of patients who had Stage II disease with low-grade or high-grade tumor budding was compared with that of 226 patients who had Stage III colon cancer. Univariate analysis revealed that serosal surface involvement (P = 0.04) and tumor budding (P < 0.001) were significantly related to survival. Cumulative five- and ten-year survival rates differed significantly between patients with low-grade tumor budding (93.9 and 90.6 percent, respectively) and those with high-grade (73.9 and 67.8 percent, respectively). Survival rates did not differ significantly between patients with Stage II disease who had high-grade tumor budding and patients with Stage III disease. Cox's regression analysis demonstrated that tumor budding (hazard ratio, 4.89; P < 0.001) and serosal surface involvement (hazard ratio, 2.561; P = 0.023) were independent prognostic factors. Liver (P < 0.001) and peritoneal (P = 0.003) metastases were more frequent in the patients with high-grade tumor budding than in those with low-grade. Tumor budding is useful for prognosis and identifying patients with Stage II colon cancer who have a high risk of disease recurrence after curative surgery.