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Makorin Ring Finger Protein 1 as Adjunctive Marker in Liquid-based Cervical Cytology

 Maria Lee  ;  Min Young Chang  ;  Ha-Yeon Shin  ;  Eunah Shin  ;  Sun Won Hong  ;  Kyung-Mi Kim  ;  Doo Byung Chay  ;  Hanbyoul Cho  ;  Jae-Hoon Kim 
 MEDICINE, Vol.95(3) : 2425, 2016 
Journal Title
Issue Date
Adult ; Biomarkers, Tumor/metabolism* ; Cervical Intraepithelial Neoplasia/diagnosis* ; Cervical Intraepithelial Neoplasia/metabolism ; Cervical Intraepithelial Neoplasia/virology ; Cervix Uteri/pathology ; Cervix Uteri/virology ; Cyclin-Dependent Kinase Inhibitor p16 ; Early Detection of Cancer/methods* ; False Positive Reactions ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Neoplasm Proteins/metabolism ; Nerve Tissue Proteins/metabolism* ; Papillomaviridae/genetics ; Papillomaviridae/isolation & purification ; Papillomavirus Infections/diagnosis* ; Papillomavirus Infections/metabolism ; Papillomavirus Infections/virology ; Predictive Value of Tests ; Prospective Studies ; Real-Time Polymerase Chain Reaction ; Retrospective Studies ; Ribonucleoproteins/metabolism* ; Sensitivity and Specificity ; Uterine Cervical Neoplasms/diagnosis* ; Uterine Cervical Neoplasms/metabolism ; Uterine Cervical Neoplasms/virology
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.
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1. College of Medicine (의과대학) > Dept. of Obstetrics and Gynecology (산부인과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
Yonsei Authors
Kim, Jae Hoon(김재훈) ORCID logo https://orcid.org/0000-0001-6599-7065
Chang, Min Young(장민영)
Cho, Hanbyoul(조한별) ORCID logo https://orcid.org/0000-0002-6177-1648
Chay, Doo Byung(채두병) ORCID logo https://orcid.org/0000-0002-0648-4021
Hong, Soon Won(홍순원) ORCID logo https://orcid.org/0000-0002-0324-2414
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