title: Automated tumor analysis for molecular profiling in lung cancer.
abstract: The discovery and clinical application of molecular biomarkers in solid tumors, increasingly relies on nucleic acid extraction from FFPE tissue sections and subsequent molecular profiling. This in turn requires the pathological review of haematoxylin & eosin (H&E) stained slides, to ensure sample quality, tumor DNA sufficiency by visually estimating the percentage tumor nuclei and tumor annotation for manual macrodissection. In this study on NSCLC, we demonstrate considerable variation in tumor nuclei percentage between pathologists, potentially undermining the precision of NSCLC molecular evaluation and emphasising the need for quantitative tumor evaluation. We subsequently describe the development and validation of a system called TissueMark for automated tumor annotation and percentage tumor nuclei measurement in NSCLC using computerized image analysis. Evaluation of 245 NSCLC slides showed precise automated tumor annotation of cases using Tissuemark, strong concordance with manually drawn boundaries and identical EGFR mutational status, following manual macrodissection from the image analysis generated tumor boundaries. Automated analysis of cell counts for % tumor measurements by Tissuemark showed reduced variability and significant correlation (p < 0.001) with benchmark tumor cell counts. This study demonstrates a robust image analysis technology that can facilitate the automated quantitative analysis of tissue samples for molecular profiling in discovery and diagnostics.
authors: Centre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast, UK.|PathXL Ltd, Northern Ireland Science Park, Belfast, UK.
authors: Peter W
authors: PW
authors: Hamilton
authors: Centre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast, UK.|PathXL Ltd, Northern Ireland Science Park, Belfast, UK.
authors: Yinhai
authors: Y
authors: Wang
authors: Department of Cellular and Molecular Pathology, Antrim Area Hospital, Antrim, UK.
authors: Clinton
authors: C
authors: Boyd
authors: Centre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast, UK.
authors: Jacqueline A
authors: JA
authors: James
authors: Institute of Pathology, Royal Victoria Hospital, Belfast, UK.|Centre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast, UK.
authors: Maurice B
authors: MB
authors: Loughrey
authors: Institute of Pathology, Royal Victoria Hospital, Belfast, UK.
authors: Joseph P
authors: JP
authors: Hougton
authors: Centre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast, UK.
authors: David P
authors: DP
authors: Boyle
authors: Institute of Pathology, Royal Victoria Hospital, Belfast, UK.
authors: Paul
authors: P
authors: Kelly
authors: Centre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast, UK.
authors: Perry
authors: P
authors: Maxwell
authors: Institute of Pathology, Royal Victoria Hospital, Belfast, UK.
authors: David
authors: D
authors: McCleary
authors: Institute of Pathology, Royal Victoria Hospital, Belfast, UK.
authors: James
authors: J
authors: Diamond
authors: Centre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast, UK.
authors: Darragh G
authors: DG
authors: McArt
authors: Institute of Pathology, Royal Victoria Hospital, Belfast, UK.
authors: Jonathon
authors: J
authors: Tunstall
authors: Centre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast, UK.
authors: Peter
authors: P
authors: Bankhead
authors: Centre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast, UK.|Institute of Pathology, Royal Victoria Hospital, Belfast, UK.
authors: Manuel
authors: M
authors: Salto-Tellez
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis*; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology*; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D008175:Lung Neoplasms / Q000473:pathology*; D015588:Observer Variation; D010363:Pattern Recognition, Automated / Q000379:methods*; D060388:Support Vector Machine
chemical_list: D014408:Biomarkers, Tumor
keywords: digital pathology; image analysis; manual macrodissection; molecular pathology; percentage tumor