Tumour budding: a promising parameter in colorectal cancer

Abstract

In 2011, the Tumour Node Metastasis (TNM) staging system still remains the gold standard for stratifying colorectal cancer (CRC) patients into prognostic subgroups, and is considered a solid basis for treatment management. Nevertheless, there is still a challenge with regard to therapeutic strategy; stage II patients are not typically selected for postoperative adjuvant chemotherapy, although some stage II patients have a comparable outcome to stage III patients who, themselves do receive such treatment. Consequently, there has been an inundation of ‘prognostic biomarker' studies aiming to improve the prognostic stratification power of the TNM staging system. Most proposed biomarkers are not implemented because of lack of reproducibility, validation and standardisation. This problem can be partially resolved by following the REMARK guidelines. In search of novel prognostic factors for patients with CRC, one might glance at a table in the book entitled ‘Prognostic Factors in Cancer' published by the International Union against Cancer (UICC) in 2006, in which TNM stage, L and V classifications are considered ‘essential' prognostic factors, whereas tumour grade, perineural invasion, tumour budding and tumour-border configuration among others are proposed as ‘additional' prognostic factors. Histopathology reports normally include the ‘essential' features and are accompanied by tumour grade, histological subtype and information on perineural invasion, but interestingly, the tumour-border configuration (i.e., growth pattern) and especially tumour budding are rarely reported. Although scoring systems such as the ‘BRE' in breast and ‘Gleason' in prostate cancer are solidly based on histomorphological features and used in daily practice, no such additional scoring system to complement TNM staging is available for CRC. Regardless of differences in study design and methods for tumour-budding assessment, the prognostic power of tumour budding has been confirmed by dozens of study groups worldwide, suggesting that tumour budding may be a valuable candidate for inclusion into a future prognostic scoring system for CRC. This mini-review therefore attempts to present a short and concise overview on tumour budding, including morphological, molecular and prognostic aspects underlining its inter-disciplinary relevance.

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

“…field" and "10 high power field" methods) [11][12][13][14][15][16]18 . Counting across multiple fields has the advantage of being more representative of the entire invasive front, and there is also some evidence of improved inter-observer agreement using this approach [11][12][13][14][15][16]18,45 . On the other hand, counting multiple fields may "dilute" the final (mean) tumor bud count in cases with focally many tumor buds The "hotspot" method therefore better reflects the maximal extent of tumor budding at the invasive front.…”

“…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.…”

“…One of the main reasons that tumor budding is not routinely reported is the lack of a standardized scoring system that is simple and reproducible 11,12 . 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.…”

“…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.…”