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.

Prognostic Impact of Tumor Budding on Moroccan Gastric Cancer Patients

“…Tumor budding is one of the parameters that need to be introduced in the management of gastric cancer since it has been defined as an independent prognostic factor in gastrointestinal carcinomas like colon cancer. 5 Tumor budding is defined as the presence of single tumor cells or clusters of up to 4 cells at the tumor invasive front (peritumoral budding, PTB) or the tumor center (intratumoral budding, ITB). [6][7][8] Many recent studies, have demonstrated that high tumor budding correlates with unfavorable clinicopathological features (stage, lymph node metastases, distant metastases, and perineural invasion) in colorectal cancer.…”

“…[6][7][8] Many recent studies, have demonstrated that high tumor budding correlates with unfavorable clinicopathological features (stage, lymph node metastases, distant metastases, and perineural invasion) in colorectal cancer. 5,7 Moreover, TB is recognized as an independent prognostic factor in CRC by the International Tumor Budding Consensus Conference (ITBCC), and is officially defined as a prognostic hallmark by the Union for International Cancer Control (UICC). [9][10][11] Currently, the prognostic value of tumor budding in gastric cancer has not been well established.…”

“…Tumor budding is one of the parameters that need to be introduced in the management of gastric cancer since it has been defined as an independent prognostic factor in gastrointestinal carcinomas like colon cancer. 5…”

Preoperative prediction of tumor budding in rectal cancer using multiple machine learning algorithms based on MRI T2WI radiomics

“…TB,as a process of epithelial-mesenchymal transition in tumors ( 9 , 10 ), was recommended by the International Tumor Budding Consensus Conference (ITBCC) in 2016 to be included in the guidelines/protocols and staging systems for rectal cancer pathology reporting. It also provided a definition for tumor budding ( 11 ). TB refers to the presence of scattered tumor cells or small clusters of tumor cells with poor differentiation at the invasive front of the tumor, observed under high-power microscopy.…”

“…TB is categorized into three grades based on the number of buds: low-grade budding (Budding1, Bd1) with 0-4 buds, intermediate-grade budding (Bd2) with 5-9 buds, and high-grade budding (Bd3) with ≥10 buds (within a 20x visual field, corresponding to an area of 0.785 mm²). High-grade budding has been significantly associated with reduced overall survival rate, adverse clinical-pathological features, invasive growth patterns, lymph node metastasis and tumor recurrence rate ( 4 , 8 ) ( 11 – 14 ). The AJCC/UICC cancer staging guidelines have included tumor budding as an additional prognostic factor for rectal cancer ( 9 ).…”