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

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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 INK4a. 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.

Original languageEnglish
Article numbere2425
JournalMedicine (United States)
Volume95
Issue number3
DOIs
Publication statusPublished - 2016

All Science Journal Classification (ASJC) codes

  • Medicine(all)

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    Lee, M., Chang, M. Y., Shin, H. Y., Shin, E., Hong, S. W., Kim, K. M., Chay, D. B., Cho, H., & Kim, J. H. (2016). Makorin ring finger protein 1 as adjunctive marker in liquid-based cervical cytology. Medicine (United States), 95(3), [e2425]. https://doi.org/10.1097/MD.0000000000002425