title: Makorin Ring Finger Protein 1 as Adjunctive Marker in Liquid-based Cervical Cytology.
abstract: To assess the utility of makorin ring finger protein 1 (MKRN1) as a marker of cervical pathology.A PROspective specimen collection and retrospective Blinded Evaluation study was conducted. Liquid-based cytology samples were collected from 187 women, embedding all residuals as cell blocks for immunohistochemical staining of MKRN1 and P16 . Results of liquid-based cervical cytology, immunostained cell block sections, and human papillomavirus (HPV) hybrid capture (with real-time polymerase chain reaction) were analyzed. Clinical outcomes were analyzed overall and in subsets of specimens yielding atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesions.Makorin ring finger protein 1 positivity and grades (1-3) of cervical intraepithelial neoplasia (CIN) increased in tandem (CIN1, 32.4%; CIN2, 60.0%; and CIN3, 80.0%), reaching 92.3% in invasive cancer. Sensitivity, specificity, positive predictive value, and negative predictive value in detecting CIN2+ via MKRN1 were 73.8%, 76.8%, 75.6%, and 75.0%, respectively. The performance of liquid-based cytology was poorer by comparison (61.3%, 69.5%, 66.2%, and 64.8%, respectively), and HPV assay (versus MKRN1 immunohistochemical staining) displayed lower specificity (67.7%). Combined HPV + MKRN1 testing proved highest in sensitivity, specificity, positive predictive value, and negative predictive value (71.8%, 85.5%, 82.3%, and 76.5%, respectively), whereas corresponding values for cytology + HPV (60.6%, 81.8%, 75.4%, and 69.2%) and cytology + MKRN1 (58.8%, 84.1%, 78.3%, and 67.7%) were all similar. In instances of atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesions, the HPV + MKRN1 combination performed best by above measures (100%, 72.7%, 73.9%, and 100%), followed by cytology + MKRN1 (100%, 50.0%, 60.7%, and 100%).Makorin ring finger protein 1 displayed greater sensitivity and specificity than liquid-based cytology and proved more specific than HPV assay. In combination testing, MKRN1 + HPV showed the highest sensitivity and specificity levels. The MKRN1 biomarker may be a useful adjunct in primary cervical cytology screening.
authors.affiliation: From the Department of Obstetrics and Gynecology, Seoul National University College of Medicine (ML), Department of Obstetrics and Gynecology, Gangnam Severance Hospital, Yonsei University College of Medicine (MYC, H-YS, DBC, HBC, J-HK), Department of Pathology, CHA Gangnam Medical Center, CHA University (ES), Department of Pathology, Yonsei University College of Medicine (SWH); and Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea (K-MK).
authors.forename: Maria
authors.initials: M
authors.lastname: Lee
authors.forename: Min Young
authors.initials: MY
authors.lastname: Chang
authors.forename: Ha-Yeon
authors.initials: HY
authors.lastname: Shin
authors.forename: Eunah
authors.initials: E
authors.lastname: Shin
authors.forename: Sun Won
authors.initials: SW
authors.lastname: Hong
authors.forename: Kyung-Mi
authors.initials: KM
authors.lastname: Kim
authors.forename: Doo Byung
authors.initials: DB
authors.lastname: Chay
authors.forename: Hanbyoul
authors.initials: H
authors.lastname: Cho
authors.forename: Jae-Hoon
authors.initials: JH
authors.lastname: Kim
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002584:Cervix Uteri / Q000473:pathology / Q000821:virology; D019941:Cyclin-Dependent Kinase Inhibitor p16; D055088:Early Detection of Cancer / Q000379:methods*; D005189:False Positive Reactions; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D027383:Papillomaviridae / Q000235:genetics / Q000302:isolation & purification; D030361:Papillomavirus Infections / Q000175:diagnosis* / Q000378:metabolism / Q000821:virology; D011237:Predictive Value of Tests; D011446:Prospective Studies; D060888:Real-Time Polymerase Chain Reaction; D012189:Retrospective Studies; D012261:Ribonucleoproteins / Q000378:metabolism*; D012680:Sensitivity and Specificity; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000821:virology; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis* / Q000378:metabolism / Q000821:virology
chemical_list: D014408:Biomarkers, Tumor; C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; C410808:Makorin ring finger protein 1; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D012261:Ribonucleoproteins
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