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Comprehensive assessment of tumour budding by cytokeratin staining in colorectal cancer


Rieger, Gregor; Koelzer, Viktor H; Dawson, Heather E; Berger, Martin D; Hädrich, Marion; Inderbitzin, Daniel; Lugli, Alessandro; Zlobec, Inti (2017). Comprehensive assessment of tumour budding by cytokeratin staining in colorectal cancer. Histopathology, 70(7):1044-1051.

Abstract

Aims Tumour budding in colorectal cancer (CRC) is a recognized prognostic parameter. The aim of this study was to address the use of cytokeratin immunostaining for the visualization and scoring of tumour buds.
Methods and results Ten hotspots (0.238 mm2) of peritumoural budding (PTB) and intratumoural budding (ITB) were evaluated in surgical resections from 215 patients. The budding counts in the 10 densest regions anywhere in the tumour were combined into an overall tumour budding (OTB) score. The PTB, ITB and OTB hotspot with the maximum budding count was then evaluated. Finally, continuous and cut‐off values of 10 buds per high‐power field (HPF) (PTB10HPF), five buds per HPF (ITB10HPF) and eight buds per HPF (OTB10HPF) were used to categorize budding counts into low‐grade and high‐grade scores. All budding scores were highly correlated. PTB and ITB counts were associated with many clinicopathological features, including tumour stage, lymph node and distant metastasis, venous and lymphovascular invasion, and disease‐free survival (DFS) (all P < 0.05). Analyses of OTB counts recapitulated these associations, including a lower DFS with a greater number of tumour buds (P = 0.0309; hazard ratio 1.0332, 95% confidence interval 1.003–1.062). One OTB hotspot performed similarly to 10 OTB hotspots in terms of relationship with outcome. These statistical significances were largely lost when cut‐offs were applied to PTB, ITB or OTB counts.
Conclusions An OTB count in a single hotspot on cytokeratin‐stained CRC tissue sections is a fast and reliable prognostic scoring system for the assessment of tumour budding. This approach should be considered in future studies.

Abstract

Aims Tumour budding in colorectal cancer (CRC) is a recognized prognostic parameter. The aim of this study was to address the use of cytokeratin immunostaining for the visualization and scoring of tumour buds.
Methods and results Ten hotspots (0.238 mm2) of peritumoural budding (PTB) and intratumoural budding (ITB) were evaluated in surgical resections from 215 patients. The budding counts in the 10 densest regions anywhere in the tumour were combined into an overall tumour budding (OTB) score. The PTB, ITB and OTB hotspot with the maximum budding count was then evaluated. Finally, continuous and cut‐off values of 10 buds per high‐power field (HPF) (PTB10HPF), five buds per HPF (ITB10HPF) and eight buds per HPF (OTB10HPF) were used to categorize budding counts into low‐grade and high‐grade scores. All budding scores were highly correlated. PTB and ITB counts were associated with many clinicopathological features, including tumour stage, lymph node and distant metastasis, venous and lymphovascular invasion, and disease‐free survival (DFS) (all P < 0.05). Analyses of OTB counts recapitulated these associations, including a lower DFS with a greater number of tumour buds (P = 0.0309; hazard ratio 1.0332, 95% confidence interval 1.003–1.062). One OTB hotspot performed similarly to 10 OTB hotspots in terms of relationship with outcome. These statistical significances were largely lost when cut‐offs were applied to PTB, ITB or OTB counts.
Conclusions An OTB count in a single hotspot on cytokeratin‐stained CRC tissue sections is a fast and reliable prognostic scoring system for the assessment of tumour budding. This approach should be considered in future studies.

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Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Institute of Pathology and Molecular Pathology
Dewey Decimal Classification:610 Medicine & health
Scopus Subject Areas:Health Sciences > Pathology and Forensic Medicine
Health Sciences > Histology
Language:English
Date:2017
Deposited On:26 Sep 2019 13:11
Last Modified:28 Jul 2020 14:13
Publisher:Wiley-Blackwell Publishing, Inc.
ISSN:0309-0167
OA Status:Green
Publisher DOI:https://doi.org/10.1111/his.13164
PubMed ID:28061021

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