Evaluation of the usefulness of tumor budding on the prediction of metastasis to the lung and liver after curative excision of colorectal cancer

BACKGROUND/AIMS: We evaluated the usefulness of tumor budding, defined as the morphology of infiltration by small clusters of undifferentiated adenocarcinoma into the invasive front of the lesion, for the prediction of metastasis to the lung and liver after curative excision of colorectal cancer. METHODOLOGY: The subjects were 491 patients with a single colorectal cancer lesion, in whom follow-up observation was performed for more than 5 years, consisting of 278 patients without recurrence, 155 patients with the first metastasis to the liver alone, and 58 patients with the first metastasis to the lung alone. The invasive front was histologically re-examined using sections with the largest diameter of the primary colorectal cancer lesion, and the tumor budding was classified into 3 grades based on the morphology of infiltration. The usefulness of this factor for the prediction of metastasis to the lung and liver was examined by multivariate analysis together with conventional clinicopathological factors such as age, sex, tumor location, tumor size, histological type, tumor depth, invasion of lymph ducts, venous invasion, and metastasis to lymph nodes. RESULTS: Comparisons of the no-recurrence and lung metastasis groups by multivariate analysis indicated that moderate to severe tumor budding (odds ratio=0.1291, P<0.0001) and positive metastasis to lymph nodes (odds ratio=0.1142, P<0.0001) were extracted as the independent prediction factors of metastasis to the lung. Comparisons of the no-recurrence and liver metastasis groups indicated that infiltration over the proper muscular tunics (odds ratio=0.0284, P<0.0001) and positive metastasis to lymph nodes (odds ratio=0.3289, P=0.0002) were extracted as the independent prediction factors of metastasis to the liver. CONCLUSIONS: Tumor budding in the invasive front of the lesion was considered to be a simple and useful pathohistological factor for the prediction of metastasis to the lung in patients with colorectal cancer after curative excision. It was suggested that this factor is important for the prediction of metastasis to the lung after surgery and for the planning of treatment methods.