Independent prognostic significance of tumor budding and poorly differentiated clusters in Brazilian patients with stage II colorectal cancer

Abstract Background Colorectal cancer (CRC) is the third most commonly diagnosed and the second most fatal cancer worldwide. Tumor budding (TB) and poorly differentiated clusters (PDC) are morphological features with significant prognostic value that may aid therapeutic decisions, particularly in st...

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Main Authors: Monise Tadin Reis, Marcus Matsushita, Wellington Santos, Gustavo Noriz Berardinelli, Valiana Teodoro, Mariana Bisarro dos Reis, Denise Peixoto Guimarães, Rui Manuel Reis
Format: Article
Language:English
Published: BMC 2025-08-01
Series:Surgical and Experimental Pathology
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Online Access:https://doi.org/10.1186/s42047-025-00196-2
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author Monise Tadin Reis
Marcus Matsushita
Wellington Santos
Gustavo Noriz Berardinelli
Valiana Teodoro
Mariana Bisarro dos Reis
Denise Peixoto Guimarães
Rui Manuel Reis
author_facet Monise Tadin Reis
Marcus Matsushita
Wellington Santos
Gustavo Noriz Berardinelli
Valiana Teodoro
Mariana Bisarro dos Reis
Denise Peixoto Guimarães
Rui Manuel Reis
author_sort Monise Tadin Reis
collection DOAJ
description Abstract Background Colorectal cancer (CRC) is the third most commonly diagnosed and the second most fatal cancer worldwide. Tumor budding (TB) and poorly differentiated clusters (PDC) are morphological features with significant prognostic value that may aid therapeutic decisions, particularly in stage II patients. The present study aimed to determine the prognostic role of TB and PDC in a Brazilian population. Methods TB and PDC were evaluated on H&E slides according to International Tumor Budding Consensus Conference (ITBCC) guidelines in 257 stage II primary colorectal cancer patients, characterized for microsatellite instability (MSI) and BRAF V600E mutation. Clinicopathological, molecular associations, five and 10-year disease-specific survival (DSS), and disease-free survival (DFS) were evaluated. Results High TB and/or high PDC were associated with clinicopathological features of aggressiveness, such as angiolymphatic invasion, recurrence or metastasis, perineural invasion, BRAF V600E mutation, and MSI-H tumors. Patients with high TB and high PDC have lower DSS and DFS compared with low TB and low PDC, and the survival was even lower when patients did not receive adjuvant chemotherapy. On a multivariate Cox Regression analysis, patients with high TB had a higher risk of recurrence or metastasis (HR = 4.213), and patients with high PDC had a significantly higher risk of death by cancer (HR = 4.181). Conclusions TB and PDC are independent prognostic factors in stage II Brazilian patients with CRC and must be considered when making therapeutic decisions.
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spelling doaj-art-2019258f6aca4f1b8b649ef59ebb7f462025-08-20T04:01:56ZengBMCSurgical and Experimental Pathology2520-84542025-08-018111210.1186/s42047-025-00196-2Independent prognostic significance of tumor budding and poorly differentiated clusters in Brazilian patients with stage II colorectal cancerMonise Tadin Reis0Marcus Matsushita1Wellington Santos2Gustavo Noriz Berardinelli3Valiana Teodoro4Mariana Bisarro dos Reis5Denise Peixoto Guimarães6Rui Manuel Reis7Department of Pathology, Barretos Cancer HospitalDepartment of Pathology, Barretos Cancer HospitalMolecular Oncology Research Center, Barretos Cancer HospitalMolecular Oncology Research Center, Barretos Cancer HospitalDepartment of Epidemiology and Biostatistics, Barretos Cancer HospitalMolecular Oncology Research Center, Barretos Cancer HospitalMolecular Oncology Research Center, Barretos Cancer HospitalMolecular Oncology Research Center, Barretos Cancer HospitalAbstract Background Colorectal cancer (CRC) is the third most commonly diagnosed and the second most fatal cancer worldwide. Tumor budding (TB) and poorly differentiated clusters (PDC) are morphological features with significant prognostic value that may aid therapeutic decisions, particularly in stage II patients. The present study aimed to determine the prognostic role of TB and PDC in a Brazilian population. Methods TB and PDC were evaluated on H&E slides according to International Tumor Budding Consensus Conference (ITBCC) guidelines in 257 stage II primary colorectal cancer patients, characterized for microsatellite instability (MSI) and BRAF V600E mutation. Clinicopathological, molecular associations, five and 10-year disease-specific survival (DSS), and disease-free survival (DFS) were evaluated. Results High TB and/or high PDC were associated with clinicopathological features of aggressiveness, such as angiolymphatic invasion, recurrence or metastasis, perineural invasion, BRAF V600E mutation, and MSI-H tumors. Patients with high TB and high PDC have lower DSS and DFS compared with low TB and low PDC, and the survival was even lower when patients did not receive adjuvant chemotherapy. On a multivariate Cox Regression analysis, patients with high TB had a higher risk of recurrence or metastasis (HR = 4.213), and patients with high PDC had a significantly higher risk of death by cancer (HR = 4.181). Conclusions TB and PDC are independent prognostic factors in stage II Brazilian patients with CRC and must be considered when making therapeutic decisions.https://doi.org/10.1186/s42047-025-00196-2Colorectal cancerTumor buddingPoorly differentiated clusterPrognostic factorDisease-specific survivalDisease-free survival
spellingShingle Monise Tadin Reis
Marcus Matsushita
Wellington Santos
Gustavo Noriz Berardinelli
Valiana Teodoro
Mariana Bisarro dos Reis
Denise Peixoto Guimarães
Rui Manuel Reis
Independent prognostic significance of tumor budding and poorly differentiated clusters in Brazilian patients with stage II colorectal cancer
Surgical and Experimental Pathology
Colorectal cancer
Tumor budding
Poorly differentiated cluster
Prognostic factor
Disease-specific survival
Disease-free survival
title Independent prognostic significance of tumor budding and poorly differentiated clusters in Brazilian patients with stage II colorectal cancer
title_full Independent prognostic significance of tumor budding and poorly differentiated clusters in Brazilian patients with stage II colorectal cancer
title_fullStr Independent prognostic significance of tumor budding and poorly differentiated clusters in Brazilian patients with stage II colorectal cancer
title_full_unstemmed Independent prognostic significance of tumor budding and poorly differentiated clusters in Brazilian patients with stage II colorectal cancer
title_short Independent prognostic significance of tumor budding and poorly differentiated clusters in Brazilian patients with stage II colorectal cancer
title_sort independent prognostic significance of tumor budding and poorly differentiated clusters in brazilian patients with stage ii colorectal cancer
topic Colorectal cancer
Tumor budding
Poorly differentiated cluster
Prognostic factor
Disease-specific survival
Disease-free survival
url https://doi.org/10.1186/s42047-025-00196-2
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