Development of a semi-automated method for tumour budding assessment in colorectal cancer and comparison with manual methods

Natalie C Fisher, Maurice B Loughrey, Helen G Coleman, Melvin D Gelbard, Peter Bankhead, Philip D Dunne

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Abstract

Aims: Tumour budding (TB) is an established prognostic feature in multiple cancers but is not routinely assessed in pathology practice. Efforts to standardise and automate assessment have shifted from haematoxylin and eosin (H&E)-stained images towards cytokeratin immunohistochemistry. The aim of this study was to compare manual H&E and cytokeratin assessment methods with a semi-automated approach built within QuPath open-source software. Methods and results: TB was assessed in cores from the advancing tumour edge in a cohort of stage II/III colon cancers (n = 186). The total numbers of buds detected with each method were as follows: manual H&E, n = 503; manual cytokeratin, n = 2290; and semi-automated, n = 5138. More than four times the number of buds were identified manually with cytokeratin assessment than with H&E assessment. One thousand seven hundred and thirty-four individual buds were identified with both manual and semi-automated assessments applied to cytokeratin images, representing 75.7% of the buds identified manually (n = 2290) and 33.7% of the buds detected with the semi-automated method (n = 5138). Higher semi-automated TB scores were due to any discrete area of cytokeratin immunopositivity within an accepted area range being identified as a bud, regardless of shape or crispness of definition, and to the inclusion of tumour cell clusters within glandular lumina (‘luminal pseudobuds’). Although absolute numbers differed, semi-automated and manual bud counts were strongly correlated across cores (ρ = 0.81, P < 0.0001). All methods of TB assessment demonstrated poorer survival associated with higher TB scores. Conclusions: We present a new QuPath-based approach to TB assessment, which compares favourably with established methods and offers a freely available, rapid and transparent tool that is also applicable to whole slide images.

Original languageEnglish
Pages (from-to)485-500
Number of pages16
JournalHistopathology
Volume80
Issue number3
Early online date28 Sept 2021
DOIs
Publication statusPublished - Feb 2022

Bibliographical note

Funding Information:
The study cohort creation was enabled by funding from Cancer Research UK (ref. C37703/A15333 and C50104/A17592) and a Northern Ireland HSC R&D Doctoral Research Fellowship (ref. EAT/4905/13). This work was supported by the Queens University Belfast Foundation (P. D. Dunne and N. C. Fisher; Musgrave scholarship), a Cancer Research UK early detection grant (P. D. Dunne; A29834), a Cancer Research UK Career Establishment Award (H. G. Coleman; C37703/A25820), and the Chan Zuckerberg Initiative DAF, an advised fund of Silicon Valley Community Foundation (awarded to P. Bankhead; M. D. Gelbard was funded by grant number 2019‐207148).

Funding Information:
The study cohort creation was enabled by funding from Cancer Research UK (ref. C37703/A15333 and C50104/A17592) and a Northern Ireland HSC R&D Doctoral Research Fellowship (ref. EAT/4905/13). This work was supported by the Queens University Belfast Foundation (P. D. Dunne and N. C. Fisher; Musgrave scholarship), a Cancer Research UK early detection grant (P. D. Dunne; A29834), a Cancer Research UK Career Establishment Award (H. G. Coleman; C37703/A25820), and the Chan Zuckerberg Initiative DAF, an advised fund of Silicon Valley Community Foundation (awarded to P. Bankhead; M. D. Gelbard was funded by grant number 2019-207148). The samples used in this research were received from the Northern Ireland Biobank, which has received funds from HSC Research and Development Division of the Public Health Agency in Northern Ireland and the Friends of the Cancer Centre. The Belfast Health and Social Care Trust Department of Cellular Pathology is acknowledged for assisting with immunohistochemistry.

Publisher Copyright:
© 2021 The Authors. Histopathology published by John Wiley & Sons Ltd

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology

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