Construction and analysis of tissue microarrays in the era of digital pathology: a pilot study targeting CDX1 and CDX2 in a colon cancer cohort of 612 patients.

作者: Sarah Nolte , Inti Zlobec , Alessandro Lugli , Werner Hohenberger , Roland Croner

DOI: 10.1002/CJP2.62

关键词: HistologyTumour heterogeneityImmunohistochemistryColorectal cancerCohortDigital pathologyTissue microarrayPathologyBiologyBiomarker Analysis

摘要: CDX1 and CDX2 are possibly predictive biomarkers in colorectal cancer. We combined digitally-guided (next generation) TMA construction (ngTMA) the utility of digital image analysis (DIA) to assess accuracy, tumour heterogeneity selective impact different intensity-percentage levels on prognosis.CDX1 immunohistochemistry was performed ngTMAs covering normal tissue, centre invasive front. The percentages all epithelial cells per staining intensity core were analysed digitally. Beyond classical prognosis following REMARK guidelines, we investigated pre-analytical conditions, three types (mosaic-like, targeted haphazard) influences cohort segregation patient selection. ngTMA-DIA approach produced robust biomarker data with infrequent loss excellent on-target punching. detailed assessment could - except for a certain diffuse mosaic-like exclude differences between front centre, as well detect haphazard clonal heterogeneous elements. Moreover, lower counts correlated mucinous histology, higher TNM stage, grade worse survival (p < 0.01, all). Different protein expression shared comparable prognostic power great overlap combination ngTMA DIA enhances accuracy controls analysis. confirmation prognostically relevant markers CRC, this study highlights greater robustness comparison CDX1. For loss, cut-points percentage complete can be deduced recommendation.

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