High-grade intratumoral tumor budding is a predictor for lymphovascular invasion and adverse outcome in stage II colorectal cancer

PURPOSE: Evaluation of tumor budding in colorectal cancer (CRC) may help to predict the tumors' metastatic potential and patients with an aggressive tumor, although not yet metastasized at time of surgery might benefit from adjuvant therapy.

METHODS: The degree of intratumoral tumor budding (ITB) was classified as low, intermediate, and high grade according to the recommendations of the International Tumor Budding Consensus Conference (ITBCC) 2016 on H&E and pankeratin-stained TMA sections from 1262 CRC, no special type (NST), including 655 stage II CRC and was correlated to clinicopathological data and overall survival.

RESULTS: Results show that higher ITB rates are significantly linked to higher tumor grade and stage, positive nodal status, lymphovascular invasion (P < 0.0001 each), absence of peritumoral lymphocytes, infiltrating type invasive tumor margin, left-sided cancer localization, and mismatch-repair proficient cancers (P < 0.05 each). In a cohort of 655 stage II CRC, ITB was associated with lymphovascular invasion (P = 0.0459) and adverse clinical outcome (P < 0.0001). In a multivariate analysis including tumor stage, tumor grade, lymphovascular invasion, ITB, and tumor localization, only low tumor stage (P = 0.0022) and absence of lymphovascular invasion (P = 0.0043) showed independent prognostic significance.

CONCLUSION: In conclusion, our findings argue towards a clinical utility of ITB as a prognostic biomarker in stage II colorectal cancer to define patients who might benefit from adjuvant therapy. ITB might be used as additional or surrogate marker in CRC in which peritumoral tumor budding is difficult to assess.