Makorin环指蛋白1作为液基宫颈细胞学中的辅助标志物

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

作者信息

Lee Maria, Chang Min Young, Shin Ha-Yeon, Shin Eunah, Hong Sun Won, Kim Kyung-Mi, Chay Doo Byung, Cho Hanbyoul, Kim Jae-Hoon

机构信息

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).

出版信息

Medicine (Baltimore). 2016 Jan;95(3):e2425. doi: 10.1097/MD.0000000000002425.

DOI:10.1097/MD.0000000000002425

PMID:26817873

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4998247/

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.

摘要

评估 Makorin 环指蛋白 1（MKRN1）作为宫颈病变标志物的效用。开展了一项前瞻性标本采集和回顾性盲法评估研究。收集了 187 名女性的液基细胞学样本，将所有残余物包埋成细胞块用于 MKRN1 和 P16 的免疫组织化学染色。分析了液基宫颈细胞学、免疫染色细胞块切片以及人乳头瘤病毒（HPV）杂交捕获（实时聚合酶链反应）的结果。对总体临床结果以及产生意义不明确的非典型鳞状细胞或低级别鳞状上皮内病变的标本亚组进行了分析。宫颈上皮内瘤变（CIN）的 Makorin 环指蛋白 1 阳性率和分级（1 - 3 级）呈同步增加（CIN1，32.4%；CIN2，60.0%；CIN3，80.0%），在浸润癌中达到 92.3%。通过 MKRN1 检测 CIN2 + 的敏感性、特异性、阳性预测值和阴性预测值分别为 73.8%、76.8%、75.6%和 75.0%。相比之下，液基细胞学的表现较差（分别为 61.3%、69.5%、66.2%和 64.8%），HPV 检测（与 MKRN1 免疫组织化学染色相比）显示出较低的特异性（67.7%）。联合 HPV + MKRN1 检测在敏感性、特异性、阳性预测值和阴性预测值方面表现最高（分别为 71.8%、85.5%、82.3%和 76.5%），而细胞学 + HPV（60.6%、81.8%、75.4%和 69.2%）以及细胞学 + MKRN1（58.8%、84.1%、78.3%和　67.7%）的相应值均相似。在意义不明确的非典型鳞状细胞或低级别鳞状上皮内病变的情况下，HPV + MKRN1 组合在上述指标方面表现最佳（100%、72.7%、73.9%和 100%），其次是细胞学 + MKRN1（100%、50.0%、60.7%和 100%）。Makorin 环指蛋白 1 显示出比液基细胞学更高的敏感性和特异性，并且比 HPV 检测更具特异性。在联合检测中，MKRN1 + HPV 显示出最高的敏感性和特异性水平。MKRN1 生物标志物可能是原发性宫颈细胞学筛查中的一种有用辅助手段。