title: High-content imaging in cervical cancer screening.
abstract: A shift from conventional cytology to a molecular approach could improve cervical cancer screening. This proof-of-concept study aims to develop a high-content imaging platform for the simultaneous detection of multiple biomarkers for cervical disease. Liquid-based cytology (LBC) samples were used to optimize a dual ProExC/Ki-67 immunofluorescence staining protocol for SurePath-fixed cells. The simultaneous and automated detection of these biomarkers was performed using the BD Pathway 435 system. The ability of high-content imaging to detect dysplastic cervical cells was assessed using keratinocytes spiked with immunopositive SiHa cells and a high-grade squamous intraepithelial lesion (HSIL) LBC sample. The percentages of Ki-67- and ProExC-immunopositive objects correlated significantly with the percentages of spiked SiHa cells. The dysplastic cells of the HSIL sample could be detected using high-content cell analysis. In conclusion, high-content imaging allows the simultaneous and automated detection of Ki-67- and ProExC-immunopositive dysplastic cells in LBC specimens.
authors.affiliation: Applied Molecular Biology Research (AMBIOR) Group, Laboratory of Cell Biology and Histology, University of Antwerp, Antwerp, Belgium. Isabel.Micalessi@ua.ac.be
authors.forename: Maria Isabel
authors.initials: MI
authors.lastname: Micalessi
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Boulet
authors.forename: Isabel
authors.initials: I
authors.lastname: Pintelon
authors.forename: Peter
authors.initials: P
authors.lastname: Verstraelen
authors.forename: Frans
authors.initials: F
authors.lastname: Nauwelaers
authors.forename: Martin
authors.initials: M
authors.lastname: Ryser
authors.forename: Johannes
authors.initials: J
authors.lastname: Bogers
mesh_terms: D000951:Antigens, Neoplasm / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D003952:Diagnostic Imaging / Q000379:methods; D055088:Early Detection of Cancer / Q000379:methods*; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D057166:High-Throughput Screening Assays; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism; D019394:Ki-67 Antigen / Q000378:metabolism; D064111:Minichromosome Maintenance Complex Component 2; D009687:Nuclear Proteins / Q000378:metabolism; D012015:Reference Standards; D013194:Staining and Labeling; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis*; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis*
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D019394:Ki-67 Antigen; D009687:Nuclear Proteins; C084859:MCM2 protein, human; D064111:Minichromosome Maintenance Complex Component 2; D004250:DNA Topoisomerases, Type II