Tumor budding in colorectal carcinoma: time to take notice

Mitrovic, Bojana; Schaeffer, David F.; Riddell, Robert H.; Kirsch, Richard

doi:10.1038/modpathol.2012.94

Cited by 256 publications

(263 citation statements)

References 57 publications

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“…13,25,32,36 In the evaluation of budding/sprouting, we adopted the definition of Ueno et al 13 because it is widely used and has good reproducibility. 13,37 The present study originally classified budding/sprouting into grades 1, 2, and 3 based on the number of budding/sprouting foci. The two-tier grading system using low grade (corresponding to grade 1) and high grade (corresponding to grades 2 or 3) however is better for practical use because there were no significant differences between grades 2 and 3 in terms of lymph node metastasis in the present study.…”

Section: Discussionmentioning

confidence: 99%

A three-tier classification system based on the depth of submucosal invasion and budding/sprouting can improve the treatment strategy for T1 colorectal cancer: a retrospective multicenter study

et al. 2015

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More than 85% of patients with T1 colorectal cancer have no lymph node metastasis and can be cured by endoscopic resection. To avoid unnecessary surgery after complete endoscopic resection, accurate histologic methods for evaluating resected specimens are needed to discriminate those at high risk for lymph node metastasis. A retrospective multi-institutional, cross-sectional study of 806 T1 colorectal cancer patients was conducted. A budding/sprouting score was incorporated for predicting lymph node metastasis in addition to other parameters, including the depth of submucosal invasion, histologic grade, and lymphovascular invasion. Lymph node metastasis was detected in 97 patients. Independent predictors of lymph node metastasis by multivariate analysis were depth of submucosal invasion ≥ 1000 μm (odds ratio (95% confidence interval) = 5.56 (2.14-19.10)) and high-grade budding/sprouting (3.14 (1.91-5.21)). Among lesions with a depth of submucosal invasion ≥ 1000 μm, lymph node metastasis was detected in 59 (29%) of 207 patients with high-grade budding/ sprouting, and in 34 (9%) of 396 with low-grade budding/sprouting. Lymph node metastasis was detected in only 4 (2%) of 203 lesions with a depth of submucosal invasion o 1000 μm. Of these four tumors, three invaded lymphatic and/or venous vessels. Thus, the risk for lymph node metastasis can be classified into three groups: high risk with a depth of submucosal invasion ≥ 1000 μm and high-grade budding/sprouting, intermediate-risk with a depth of submucosal invasion ≥ 1000 μm and low-grade budding/sprouting, and low-risk with a depth of submucosal invasion o1000 μm. These findings revealed that a depth of submucosal invasion ≥ 1000 μm and high-grade budding/sprouting are powerful predictive parameters for lymph node metastasis in T1 colorectal cancer. This three-tier risk classification system will facilitate the decision for additional major surgery for T1 colorectal cancer patients after successful endoscopic treatment.

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Section: Discussionmentioning

confidence: 99%

A three-tier classification system based on the depth of submucosal invasion and budding/sprouting can improve the treatment strategy for T1 colorectal cancer: a retrospective multicenter study

et al. 2015

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“…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.…”

Section: Introductionmentioning

confidence: 99%

“…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.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2017

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Tumor budding is a well-established independent prognostic factor in colorectal cancer but a standardized method for its assessment has been lacking. The primary aim of the International Tumor Budding Consensus Conference (ITBCC) was to reach agreement on an international, evidence-based standardized scoring system for tumor budding in colorectal cancer.The ITBCC included 9 sessions with presentations, a pre-meeting survey, and an e-book covering the key publications on tumor budding in colorectal cancer. The "Grading of Recommendation Assessment, Development and Evaluation" method was used to determine the strength of recommendations and quality of evidence.

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“…3,4 Tumor budding at the invasive tumor margin is an established negative prognostic factor in resected colorectal cancer. [5][6][7][8][9][10][11][12] Widespread use of tumor budding as a prognostic factor has been impeded by a lack of standardized histopathological criteria, highlighted recently by Mitrovic et al 13 who state that 'although performing a tumor bud count is easy in theory, deciding what is or is not a bud can prove surprisingly difficult in practice'. Recent studies have addressed the role of tumor budding in resected colorectal specimens.…”

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confidence: 99%

Prognostic significance of tumor budding in rectal cancer biopsies before neoadjuvant therapy

et al. 2014

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Tumor budding is an increasingly important prognostic feature for pathologists to recognize. The aim of this study was to correlate intra-tumoral budding in pre-treatment rectal cancer biopsies with pathological response to neoadjuvant chemoradiotherapy and with long-term outcome. Data from a prospectively maintained database were acquired from patients with locally advanced rectal cancer who underwent neoadjuvant chemoradiotherapy. Pre-treatment rectal biopsies were retrospectively reviewed for evidence of intra-tumoral budding. Multivariate logistic regression was used to identify factors contributing to cancer-specific death, expressed as hazard ratios with 95% confidence intervals. Of the 185 patients with locally advanced rectal cancer, 89 patients met the eligibility criteria, of whom 18 (20%) exhibited budding in a pre-treatment tumor biopsy. Intra-tumoral budding predicted a poor pathological response to neoadjuvant chemoradiotherapy (higher ypT stage, P ¼ 0.032; lymph node involvement, P ¼ 0.018; lymphovascular invasion, P ¼ 0.004; and residual poorly differentiated tumors, P ¼ 0.005). No patient with intra-tumoral budding exhibited a tumor regression grade 1 or complete pathological response, providing a 100% specificity and positive predictive value for non-response to neoadjuvant chemoradiotherapy. Intra-tumoral budding was associated with a lower disease-free 5-year survival rate (33 vs 78%, Po0.001), cancer-specific 5-year survival rate (61 vs 87%, P ¼ 0.021) and predicted cancer-specific death (hazard ratio 3.51, 95% confidence interval 1.03-11.93, P ¼ 0.040). Intratumoral budding at diagnosis of rectal cancer identifies those who will poorly respond to neoadjuvant chemoradiotherapy and those with a poor prognosis.

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Tumor budding in colorectal carcinoma: time to take notice

Cited by 256 publications

References 57 publications

A three-tier classification system based on the depth of submucosal invasion and budding/sprouting can improve the treatment strategy for T1 colorectal cancer: a retrospective multicenter study

A three-tier classification system based on the depth of submucosal invasion and budding/sprouting can improve the treatment strategy for T1 colorectal cancer: a retrospective multicenter study

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

Prognostic significance of tumor budding in rectal cancer biopsies before neoadjuvant therapy

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