ArticleLaboratory investigation; a journal of technical methods and pathology2020
Digital image analysis of multiplex fluorescence IHC in colorectal cancer recognizes the prognostic value of CDX2 and its negative correlation with SOX2.
Article in Laboratory investigation; a journal of technical methods and pathology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 35 citations in OpenAlex.
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- Glutaredoxin 2 Protein (Grx2) as an Independent Prognostic Factor Associated with the Survival of Colon Adenocarcinoma Patients.International journal of molecular sciences · 2024Article
- Quantitative image analysis of intracellular protein translocation in 3-dimensional tissues for pharmacodynamic studies of immunogenic cell death.Journal of controlled release : official journal of the Controlled Release Society · 2024Article
- Inhibiting NR5A2 targets stemness in pancreatic cancer by disrupting SOX2/MYC signaling and restoring chemosensitivity.Journal of experimental & clinical cancer research : CR · 2023Article
- Accounting for intensity variation in image analysis of large-scale multiplexed clinical trial datasets.The journal of pathology. Clinical research · 2023Article
- Molecular analyses of ADAMTS-1, -4, -5, and IL-17 a cytokine relationship in patients with ulcerative colitis.BMC gastroenterology · 2023Article
- Whole-Slide Imaging, Mutual Information Registration for Multiplex Immunohistochemistry and Immunofluorescence.Laboratory investigation; a journal of technical methods and pathology · 2023Article
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- E-cadherin is a robust prognostic biomarker in colorectal cancer and low expression is associated with sensitivity to inhibitors of topoisomerase, aurora, and HSP90 in preclinical models.Molecular oncology · 2022Article
- CDX2-induced intestinal metaplasia in human gastric organoids derived from induced pluripotent stem cells.iScience · 2022Article
- Automated quantitative high-throughput multiplex immunofluorescence pipeline to evaluate OXPHOS defects in formalin-fixed human prostate tissue.Scientific reports · 2022Article
- Deep learning tools and modeling to estimate the temporal expression of cell cycle proteins from 2D still images.PLoS computational biology · 2022Article
- Immune microenvironment composition in high-grade serous ovarian cancers based on BRCA mutational status.Journal of cancer research and clinical oncology · 2021Article
- Current and Prospective Methods for Assessing Anti-Tumor Immunity in Colorectal Cancer.International journal of molecular sciences · 2021Review
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- A narrative review of digital pathology and artificial intelligence: focusing on lung cancer.Translational lung cancer research · 2020Review
- A panel of intestinal differentiation markers (CDX2, GPA33, and LI-cadherin) identifies gastric cancer patients with favourable prognosis.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2020Article
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Authors and funding
10 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Flourescence-based multiplex immunohistochemistry (mIHC) combined with multispectral imaging and digital image analysis (DIA) is a quantitative high-resolution method for determination of protein expression in tissue. We applied this method for five biomarkers (CDX2, SOX2, SOX9, E-cadherin, and β-catenin) using tissue microarrays of a Norwegian unselected series of primary colorectal cancer. The data were compared with previously obtained chromogenic IHC data of the same tissue cores, visually assessed by the Allred method. We found comparable results between the methods, although confirmed that DIA offered improved resolution to differentiate cases with high and low protein expression. However, we experienced inherent challenges with digital image analysis of membrane staining, which was better assessed visually. DIA and mIHC enabled quantitative analysis of biomarker coexpression on the same tissue section at the single-cell level, revealing a strong negative correlation between the differentiation markers CDX2 and SOX2. Both methods confirmed known prognostic associations for CDX2, but DIA improved data visualization and detection of clinicopathological and biological associations. In summary, mIHC combined with DIA is an efficient and reliable method to evaluate protein expression in tissue, here shown to recapitulate and improve detection of known clinicopathological and survival associations for the emerging biomarker CDX2, and is therefore a candidate approach to standardize CDX2 detection in pathology laboratories.
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