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Digital pattern recognition-based image analysis quantifies immune infiltrates in distinct tissue regions of colorectal cancer and identifies a metastatic phenotype
Authors:H K Angell  N Gray  C Womack  D I Pritchard  R W Wilkinson  M Cumberbatch
Institution:1.Immune Modulation Research Group, School of Pharmacy, University of Nottingham, Nottingham, UK;2.Molecular Pathology Group, AstraZeneca Pharmaceuticals, Alderley Park, Cheshire, UK;3.Oncology Innovative Medicines, AstraZeneca Pharmaceuticals, Alderley Park, Cheshire, UK
Abstract:

Background:

Several studies in colorectal cancer (CRC) indicate a relationship between tumour immune infiltrates and clinical outcome. We tested the utility of a digital pattern recognition-based image analysis (DPRIA) system to segregate tissue regions and facilitate automated quantification of immune infiltrates in CRC.

Methods:

Primary CRC with matched hepatic metastatic (n=7), primary CRC alone (n=18) and primary CRC with matched normal (n=40) tissue were analysed immunohistochemically. Genie pattern recognition software was used to segregate distinct tissue regions in combination with image analysis algorithms to quantify immune cells.

Results:

Immune infiltrates were observed predominately at the invasive margin. Quantitative image analysis revealed a significant increase in the prevalence of Foxp3 (P<0.0001), CD8 (P<0.0001), CD68 (<0.0001) and CD31 (<0.0001) positive cells in the stroma of primary and metastatic CRC, compared with tumour cell mass. A direct comparison between non-metastatic primary CRC (MET−) and primary CRC that resulted in metastasis (MET+) showed an immunosuppressive phenotype, with elevated Foxp3 (P<0.05) and reduced numbers of CD8 (P<0.05) cells in the stroma of MET+ compared with MET− samples.

Conclusion:

By combining immunohistochemistry with DPRIA, we demonstrate a potential metastatic phenotype in CRC. Our study accelerates wider acceptance and use of automated systems as an adjunct to traditional histopathological techniques.
Keywords:colorectal cancer  immunohistochemistry  image analysis  immune infiltrates  metastatic phenotype
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