Exploring Intratumoral Budding in Colorectal Cancer Using Computational Pathology: A Biopsy-Based Evaluation
Modern Pathology, vol. 38, pp. 100655
Abstract
Owing to insufficient evidence, tumor budding (TB) is not currently evaluated in colorectal cancer (CRC) biopsies. This study investigates TB in CRC by establishing the value of intratumoral budding (ITB) in resection specimens and assessing the feasibility and clinical value of TB in biopsies. TB was assessed using an algorithm in all cases. In a test cohort of 555 primarily surgically treated CRC patients, we assessed the prognostic impact of ITB compared with peritumoral budding (PTB). The distribution of ITB in the uppermost 5 mm of resection specimens was analyzed to validate TB counting in biopsies. We further validated the prognostic and predictive impact of TB in biopsies of 285 rectal cancer patients, focusing on overall survival and response to neoadjuvant therapy. High-grade TB, whether intratumoral or peritumoral and in biopsies or resections, was associated with advanced pathological stage, lymphatic invasion, infiltrative tumor border, and poor overall survival in the test cohort. Superficial ITBs (0-3 mm from the lumen) accurately predicted the final TB grade based on PTB in 87% of tumors, with 87% of tumors having at least 1 superficial ITB hotspot. ITB (hazard ratio, 3.5; 95% CI, 1.1-10.8) was an independent predictor of overall survival, unlike PTB. In the validation cohort, TB presence in biopsies significantly reduced the likelihood of achieving a pathological complete response (odds ratio, 0.3; 95% CI, 0.1-0.7; P = .007). ITB is as prognostic as PTB, and evaluating both can improve risk stratification in CRC. TB assessment in biopsies can identify poor prognosis and predict response to neoadjuvant therapy.
Authors 11
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Sonay Kuş Öztürk corresponding
Radboud University Nijmegen · Radboud University Medical Center
Affiliation as printed
Department of Pathology, Radboud University Medical Centre, Nijmegen, the Netherlands. Electronic address: sonay.kusozturk@radboudumc.nl
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Radboud University Nijmegen · Radboud University Medical Center
Affiliation as printed
Department of Pathology, Radboud University Medical Centre, Nijmegen, the Netherlands
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Affiliation as printed
Institute of Tissue Medicine and Pathology, University of Bern, Bern, Switzerland
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University College Dublin · St. Vincent's University Hospital
Affiliation as printed
Department of Pathology, St. Vincent's University Hospital, Dublin, Ireland; School of Medicine and Medical Sciences, University College Dublin, Dublin, Ireland
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Leiden University · Leiden University Medical Center
Affiliation as printed
Department of Surgery, Leiden University Medical Centre, Leiden, the Netherlands
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Corrie A.M. Marijnen Aachen
Leiden University · Leiden University Medical Center
Affiliation as printed
Department of Radiotherapy, Leiden University Medical Centre, Leiden, the Netherlands; Department of Radiotherapy, Antoni van Leeuwenhoek, Amsterdam, the Netherlands
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University Medical Center Groningen · University of Groningen
Affiliation as printed
Department of Medical Oncology, University of Groningen, University Medical Centre Groningen, Groningen, the Netherlands
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Affiliation as printed
Department of Pathology, Erasmus Medical Centre, Rotterdam, the Netherlands
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Friedrich-Alexander-Universität Erlangen-Nürnberg · Bayreuth Medical Center
Affiliation as printed
Institute of Pathology, Friedrich-Alexander-University Erlangen-Nuremberg, Klinikum Bayreuth, Bayreuth, Germany
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Affiliation as printed
Institute of Tissue Medicine and Pathology, University of Bern, Bern, Switzerland
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Radboud University Nijmegen · Radboud University Medical Center
Affiliation as printed
Department of Pathology, Radboud University Medical Centre, Nijmegen, the Netherlands
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