Prognostic Impact of Tumor Budding on Moroccan Colon Cancer Patients

Abstract

Background. Tumor budding is now emerging as one of the robust and promising histological factors that play an important role in colon cancer. In this study, we aimed to investigate the association between tumor budding and tumor clinicopathological factors, tumor molecular signature, and patient survival for the first time in a Moroccan population. Methods. We collected data of 100 patients operated from colon adenocarcinoma. Tumor budding was assessed on HES slides, according to the International Tumor Budding Consensus Conference 2016 recommendations. The expression of MMR proteins was performed by immunohistochemistry. KRAS and NRAS mutations testing was performed by Sanger sequencing and pyrosequencing. Results. High tumor budding grade (BUD 3) was found to be significantly associated with adverse clinicopathological features including older age ( $P=0.03$ ), presence of perineural invasion ( $P=0.02$ ), presence of vascular invasion ( $P=0.05$ ), distant metastases ( $P<0.001$ ), advanced TNM stage ( $P=0.001$ ), the occurrence of relapse ( $P=0.04$ ), and the high number of deceased cases ( $P=0.02$ ). Interestingly, we found that tumors with high-grade tumor budding were more likely to be microsatellite stable (MSS) ( $P=0.005$ ) and harbor more KRAS mutations ( $P=0.02$ ). Tumors with high-grade tumor budding were strongly associated with KRAS G12D mutation ( $P=0.007$ ). In all stages, high tumor budding was correlated with poorer overall survival ( $P=0.04$ ) and decreased relapse-free survival with a difference close to significance (( $P=0.09$ ). We concluded that high tumor budding was strongly associated with unfavorable clinicopathological features and special molecular biomarkers and effectively affects the overall survival of CC patients. Conclusions. Based on these findings and the ITBCC group recommendations, tumor budding should be taken into account along with other clinicopathologic factors in the risk assessment of colorectal cancer.