title: Application of flow cytometry for biomarker-based cervical cancer cells detection.
abstract: The Pap test used for cervical cancer screening is subjective, labor-intensive, and has relatively low sensitivity and specificity for the detection of underlying clinically significant lesions. The objective of this study is to develop a biomarker/flow cytometry-based approach for cervical cancer screening. Immunofluorescence technology to quantify cervical cell expression of two biomarkers p16(INK4A) and Mcm5 was developed and evaluated by both microscopy and flow cytometry. The capability of using biomarker/flow cytometry approach to detect rare-event dysplastic cells in a large background of benign epithelial and inflammatory cells was evaluated. The results indicate that flow cytometry could detect 0.01% dysplastic cells in a background of normal cervical epithelial cells with the combination of the two biomarkers. Thirty-two clinical specimens were used to test the biomarker/flow cytometry-based approach and the results were compared with the liquid-based cervical cytology. The experiment yielded 100% sensitivity and 93% specificity with reference to the liquid-based cervical cytology. This study indicates the promise of using multi-color fluorescence flow cytometry for biomarker-based cervical cancer screening. This molecular-based, potentially high-throughput and automated method is expected to provide an alternative/auxiliary means of cervical cancer screening.
authors.affiliation: Medical System Department, Automation and Data System Division, Southwest Research Institute, 6220 Culebra Road, San Antonio, TX 78238, USA. jling@swri.org
authors.forename: Jian
authors.initials: J
authors.lastname: Ling
authors.forename: Urs
authors.initials: U
authors.lastname: Wiederkehr
authors.forename: Spring
authors.initials: S
authors.lastname: Cabiness
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Shroyer
authors.forename: J Paul
authors.initials: JP
authors.lastname: Robinson
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D001706:Biopsy; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002584:Cervix Uteri / Q000378:metabolism / Q000473:pathology; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry / Q000379:methods*; D006367:HeLa Cells; D006801:Humans; D008403:Mass Screening / Q000379:methods; D012680:Sensitivity and Specificity; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000378:metabolism* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16; C489423:MCM5 protein, human