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

View Article: PubMed Central - PubMed

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.

No MeSH data available.


Related in: MedlinePlus

Immunohistochemical staining of makorin ring finger protein in representative sections of normal cervical epithelium (A) and high-grade cervical intraepithelial neoplasia (B).
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Figure 1: Immunohistochemical staining of makorin ring finger protein in representative sections of normal cervical epithelium (A) and high-grade cervical intraepithelial neoplasia (B).

Mentions: To determine MKRN1 expression, prepared cell blocks were again sectioned at 400 μm, and IHC staining was performed using rabbit anti-MKRN1 antibody and affinity purified makorin-1 antibody (Bethyl Laboratories Inc, Montgomery, TX). The UltraVision LP Detection System kit (Thermo Fisher Scientific, Fremont, CA) was used for indirect staining, using a biotin-linked secondary antibody labelled with horseradish peroxidase. The peroxidase reacts with 3,3′-diaminobenzidine tetrahydrochloride, catalyzing a color change, and the slides are counterstained with hematoxylin. Sections were interpreted by a pathology specialist, equating a positive result with visible nuclear staining (Figure 1).


Makorin Ring Finger Protein 1 as Adjunctive Marker in Liquid-based Cervical Cytology
Immunohistochemical staining of makorin ring finger protein in representative sections of normal cervical epithelium (A) and high-grade cervical intraepithelial neoplasia (B).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4998247&req=5

Figure 1: Immunohistochemical staining of makorin ring finger protein in representative sections of normal cervical epithelium (A) and high-grade cervical intraepithelial neoplasia (B).
Mentions: To determine MKRN1 expression, prepared cell blocks were again sectioned at 400 μm, and IHC staining was performed using rabbit anti-MKRN1 antibody and affinity purified makorin-1 antibody (Bethyl Laboratories Inc, Montgomery, TX). The UltraVision LP Detection System kit (Thermo Fisher Scientific, Fremont, CA) was used for indirect staining, using a biotin-linked secondary antibody labelled with horseradish peroxidase. The peroxidase reacts with 3,3′-diaminobenzidine tetrahydrochloride, catalyzing a color change, and the slides are counterstained with hematoxylin. Sections were interpreted by a pathology specialist, equating a positive result with visible nuclear staining (Figure 1).

View Article: PubMed Central - PubMed

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.

No MeSH data available.


Related in: MedlinePlus