Tumor budding is predictive of lymphatic involvement and lymph node metastases in submucosal invasive colorectal adenocarcinomas and in non-polypoid compared with polypoid growths

Objective. Early colorectal carcinomas (submucosal invasive adenocarcinomas) can be classified into polypoid and non-polypoid growth types, the latter progressing more rapidly to advanced malignancy. The aim of this study was to investigate the differences between invasive features of the two types of carcinoma by focusing on tumor budding (isolated single cells or small cell clusters (up to four cells) scattered at invasive tumor margins). Material and methods. The number of foci in the field with the most frequent tumor budding was regarded as “activity”. Tumor budding was examined using anti-cytokeratin antibodies in 98 colorectal submucosal invasive adenocarcinomas and compared with the clinicopathological findings. In addition, the relationships between tumor budding and β-catenin and laminin-5γ2 expression were analyzed. Results. Tumor budding activity was significantly higher in non-polypoid growth carcinomas compared with polypoid growth carcinomas (p = 0.0006) and values for left-sided lesions were higher than those for right-sided lesions of the colon (p = 0.0108). Positive links with tumor budding were evident for lymphatic involvement and lymph node metastasis in non-polypoid growth carcinomas, and with laminin-5γ2 cytoplasmic expression in polypoid growth carcinomas. Multivariate logistic analysis revealed that the activity of tumor budding was an independent risk factor for lymphatic involvement. Conclusions. The results indicate that tumor budding makes a greater contribution to progression in non-polypoid than in polypoid growth carcinomas, with possible involvement of lymph node metastasis.