Tumour budding in colorectal cancer: what do we know and what can we do?

Abstract

Budding is a process during which individual or small clusters of up to five tumour cells detach from the main tumour mass and invade into the surrounding stroma. In colorectal cancer, this feature is observed in 20-40% of cases and is associated with lymphovascular invasion, lymph node and distant metastases, and poor prognosis. A variety of scoring systems for budding have been proposed but so far a gold standard is lacking, hampering implementation of a budding score in guidelines for pathological examination of colorectal cancer. Furthermore, little is known about the mechanisms which cause tumour cells to detach from the main tumour mass and obtain increased invasive potential. In this review, we present an overview of tumour budding including its definition, scoring systems, prognostic relevance and biological mechanisms involved.

Recommendations for reporting tumor budding in colorectal cancer based on the International Tumor Budding Consensus Conference (ITBCC) 2016

“…1,5 . The prognostic power of tumor budding is not affected by the number of cells that defines a cluster 11,[13][14][15]18 . Since 4 tumor cells is the most widely used cut-off for tumor budding, and since this cut-off distinguishes tumor budding from the novel histopathological parameter "poorly differentiated cluster (PDC)" which is defined as 5 or more cells 27,59 , the ITBCC group agreed on a cut-off of up to 4 cells to define tumor budding reported, in accordance with current guidelines and protocols [69][70][71] .…”

“…Tumor budding is an independent adverse prognostic factor in colorectal cancer [11][12][13][14][15] . It is also associated with a higher TNM stage, high tumor grade, the presence of lymphovascular invasion and consequently with lymph node and distant metastases [11][12][13][14][15] .…”

“…It is also associated with a higher TNM stage, high tumor grade, the presence of lymphovascular invasion and consequently with lymph node and distant metastases [11][12][13][14][15] . In colorectal cancer, tumor budding can potentially be applied as an additional quantitative prognostic factor to facilitate the management of colorectal cancer patients in three clinical scenarios.…”

“…Second, in stage II colorectal cancer, the presence of tumor budding is an indicator of shorter disease-free survival compared to stage II colorectal cancer with low grade budding, or no budding. Therefore, stage II colorectal cancer patients with high grade tumor budding may be considered for adjuvant therapy 13,14,18,19 . Third, ITB assessed in preoperative biopsies could help select patients who might qualify for neo-adjuvant therapy and could potentially predict tumor regression [20][21][22] .…”

“…The selection of the tumor slide, the location of counting, the applied stain (H&E vs immunohistochemistry) and the scoring system (cut-off vs continuous scale) are practical points that need to be clarified and then validated in multiple studies. Nevertheless, tumor budding seems to be a robust biomarker which retains its prognostic value independently of selected scoring systems used in different studies [11][12][13][14][15] . The primary objective of the International Tumor Budding Consensus Conference (ITBCC), which took place in Bern in April 2016, was to reach agreement on an evidence-based, standardized scoring system for tumor budding to be used in international colorectal cancer guidelines and routine practice.…”