Biomarker expression in cervical intraepithelial neoplasia: potential progression predictive factors for low-grade lesions
Biomarker expression in cervical intraepithelial neoplasia: potential progression predictive factors for low-grade lesions
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DOI：
10.1016/j.humpath.2010.10.021
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发表时间：
2011-07-01
期刊：
影响因子：
3.3
通讯作者：
Inoue, Masaki
中科院分区：
文献类型：
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作者：
Ozaki, Satoru;Zen, Yoh;Inoue, Masaki
本研究旨在揭示3种生物标志物(p16INK4a、ProEx C和人乳头瘤病毒DNA)是否可用于宫颈上皮内瘤变的诊断，以及它们是否可以预测宫颈上皮内瘤变-1的疾病进展。我们分析了252例宫颈标本：不典型增生粘膜(n=9)、宫颈上皮内瘤变(n=229)和鳞癌(n=14)。采用p16INK4a和ProEx C免疫组织化学染色及人乳头瘤病毒DNA杂交捕获II试验。P16INK4a的表达和ProEx C在上皮内瘤变2/3(96%~100%)显著高于非增生性粘膜(11%)和上皮内瘤变1(40%~53%)。人乳头瘤病毒DNA在69%的上皮内瘤变1、95%的上皮内瘤变2和100%的上皮内瘤变3中检出。在99例有随访资料的上皮内瘤变1中，62例(73%)表现为自发消退，17例(20%)表现为持续性低级别病变，7例(7%)进展为2/3。进展组p16INK4a表达和ProEx C染色均显著高于消退组。检测p16INK4a和ProEx C对预测宫颈上皮内瘤变I进展的敏感性(86%)和中等特异性(分别为60%和61%)是高度敏感的(100%)，但特异性较低(37%)。综上所述，本研究表明p16INK4a和ProEx C是诊断宫颈上皮内瘤变的有用生物标志物，并有可能作为预测低级别病变进展的指标。(C)2011 Elsevier Inc.保留所有权利。
The aim of this study was to reveal whether 3 biomarkers (p16INK4a, ProEx C, and human papilloma virus DNA) are useful in the diagnosis of cervical intraepithelial neoplasia and whether they could predict disease progression of cervical intraepithelial neoplasia-1. We analyzed 252 cervical specimens: nondysplastic mucosa (n = 9), cervical intraepithelial neoplasia (n = 229), and squamous cell carcinoma (n = 14). Immunostaining for p16INK4a and ProEx C, and the hybridcapture II assay for human papilloma virus DNA were performed. Expression of p16INK4a and staining for ProEx C were significantly higher in intraepithelial neoplasia 2/3 (96%-100%) than in nondysplastic mucosa (11%) or intraepithelial neoplasia 1 (40%-53%). Human papilloma virus DNA was detected in 69% of intraepithelial neoplasia-1, 95% of intraepithelial neoplasia-2, and 100% of intraepithelial neoplasia 3. Of 99 patients with intraepithelial neoplasia 1 for whom follow-up data was available, 62 (73%) showed spontaneous regression, 17 (20%) demonstrated persistent low-grade lesion, and 7 (7%) progressed to intraepithelial neoplasia 2/3. Expressions of p16INK4a and staining with ProEx C were significantly higher in the progression group than in the regression group. Testing for p16INK4a and ProEx C was sensitive (86%) and moderately specific (60% and 61%, respectively) in predicting the progression of cervical intraepithelial neoplasia I. Human papilloma virus DNA testing was highly sensitive (100%) but less specific (37%). in conclusion, this study revealed that p16INK4a and ProEx C are useful biomarkers for the diagnosis of cervical intraepithelial neoplasia, and have potential as predictors of progression of low-grade lesions. (C) 2011 Elsevier Inc. All rights reserved.