Research Papers:

Novel histopathologic feature identified through image analysis augments stage II colorectal cancer clinical reporting

Peter D. Caie _, Ying Zhou, Arran K. Turnbull, Anca Oniscu and David J. Harrison

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Oncotarget. 2016; 7:44381-44394. https://doi.org/10.18632/oncotarget.10053

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Peter D. Caie1,2, Ying Zhou3, Arran K. Turnbull3, Anca Oniscu1,2, David J. Harrison1,2

1Quantitative and Digital Pathology, School of Medicine, University of St Andrews, St Andrews, KY16 9TF, UK

2Digital Pathology Unit, Laboratory Medicine, Royal Infirmary of Edinburgh, Edinburgh, EH16 4SA, UK

3Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh, EH4 2XU, UK

Correspondence to:

Peter D. Caie, email: pdc5@st-andrews.ac.uk

Keywords: digital pathology, big-data, tumor buds, poorly differentiated clusters, data mining

Received: January 13, 2016     Accepted: June 01, 2016     Published: June 15, 2016


A number of candidate histopathologic factors show promise in identifying stage II colorectal cancer (CRC) patients at a high risk of disease-specific death, however they can suffer from low reproducibility and none have replaced classical pathologic staging. We developed an image analysis algorithm which standardized the quantification of specific histopathologic features and exported a multi-parametric feature-set captured without bias. The image analysis algorithm was executed across a training set (n = 50) and the resultant big data was distilled through decision tree modelling to identify the most informative parameters to sub-categorize stage II CRC patients. The most significant, and novel, parameter identified was the ‘sum area of poorly differentiated clusters’ (AreaPDC). This feature was validated across a second cohort of stage II CRC patients (n = 134) (HR = 4; 95% CI, 1.5– 11). Finally, the AreaPDC was integrated with the significant features within the clinical pathology report, pT stage and differentiation, into a novel prognostic index (HR = 7.5; 95% CI, 3–18.5) which improved upon current clinical staging (HR = 4.26; 95% CI, 1.7– 10.3). The identification of poorly differentiated clusters as being highly significant in disease progression presents evidence to suggest that these features could be the source of novel targets to decrease the risk of disease specific death.

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