p16INK4A immunohistochemical staining and predictive value for progression of cervical intraepithelial neoplasia grade 1: A prospective study in China
p16INK4A immunohistochemical staining and predictive value for progression of cervical intraepithelial neoplasia grade 1: A prospective study in China
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DOI：
10.1002/ijc.28485
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发表时间：
2014-04-01
影响因子：
6.4
通讯作者：
Qiao, You-Lin
中科院分区：
文献类型：
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作者：
Liao, Guang-Dong;Sellors, John W.;Qiao, You-Lin
p16（INK4A）在感染人乳头瘤病毒（HPV）的妇女被诊断为宫颈上皮内瘤变（CIN）和癌症的组织中强烈表达，但很少有前瞻性研究评估p16（INK4A）作为低级别CIN （CIN1）进展风险的标志物。我们研究了p16（INK4A）免疫染色在CIN分级中的流行情况，以及p16（INK4A）在CIN1中的过表达是否能预测中国女性发生高级别CIN的未来风险。2003年至2005年，对6557名年龄在30-49岁之间的中国女性进行了细胞学和致癌HPV检测。对有异常结果的妇女进行阴道镜检查。p16（INK4A）对所有CIN1女性的活检组织进行免疫染色，以及随机选择正常或CIN2级及更差（CIN2+）活检组织的女性。CIN1的妇女在没有治疗的情况下随访。所有未经治疗的妇女每隔2年进行一次阴道镜检查。p16（INK4A）染色在正常、CIN1、cin2、cin3和癌活检中分别为2.7%、42.7%、75.5%、79.6%和100% （p < 0.001）。HPV阳性与p16（INK4A）染色密切相关[优势比(OR) = 12.8；95%置信区间（CI）： 5.2-31.6]。基线时CIN1活检的p16（INK4A）染色与随访2年后发现高级别CIN的风险增加相关（OR = 1.43; 95% CI: 0.52-3.91）。p16（INK4A）阳性妇女的两年累积CIN2+发病率为10.71%，高于p16（INK4A）阴性妇女的1.30%（粗RR = 8.25, 95% CI: 1.02-66.62）。在低级别病变的女性中，p16（INK4A）过表达与CIN的级别和进展为高级别CIN的风险密切相关。有什么新鲜事吗?与宫颈上皮内瘤变（CIN）进展为宫颈癌相关的生物标志物的发现可以允许早期开始治疗。本研究探讨了p16INK4A免疫组化染色对中国CIN 1级进展的预测价值。组织学为CIN1的女性随访2年。p16INK4A过表达的患病率随着恶性变化的严重程度而增加，因此在CIN2和CIN3女性的活检中，染色率分别为75.5%和79.6%，而CIN1为42.7%。p16INK4A的染色与人乳头瘤病毒的存在密切相关。
p16(INK4A) is strongly expressed in tissues diagnosed as cervical intraepithelial neoplasia (CIN) and cancer in women infected with human papillomavirus (HPV), but few prospective studies have evaluated p16(INK4A) as a marker for the risk of low-grade CIN (CIN1) progression. We investigated the prevalence of p16(INK4A) immunostaining by CIN grade and whether overexpression of p16(INK4A) in CIN1 predicts future risk for high-grade CIN in Chinese women. 6,557 Chinese women aged 30-49 years were screened from 2003 to 2005 using cytology and carcinogenic HPV test. Colposcopy was performed on women with any abnormal result. p16(INK4A) Immunostaining was performed on biopsies from all women with CIN1, as well as randomly selected women with normal or CIN grade 2 and worse (CIN2+) biopsies. Women with CIN1 were followed up without treatment. Colposcopy was performed on all untreated women at a 2-year interval. The prevalence of p16(INK4A) staining was 2.7%, 42.7%, 75.5%, 79.6% and 100% among women with normal, CIN1, 2, 3 and cancer biopsies, respectively (p < 0.001). HPV positivity was strongly associated with p16(INK4A) staining [odds ratios (OR) = 12.8; 95% confidence intervals (CI): 5.2-31.6]. p16(INK4A) staining of CIN1 biopsies at baseline was associated with an increased risk of finding high-grade CIN over 2 years of follow-up (OR = 1.43; 95% CI: 0.52-3.91). The two-year cumulative incidence of CIN2+ for p16(INK4A) positive women was higher at 10.71% than for p16(INK4A) negative women at 1.30% (crude RR = 8.25, 95% CI: 1.02-66.62). p16(INK4A) overexpression is strongly associated with grade of CIN and risk of progression to high-grade CIN in women with low-grade lesions.What's new? The discovery of biomarkers linked to cervical intraepithelial neoplasia (CIN) progression to cervical cancer could allow for earlier initiation of treatment. This study examined the predictive value of p16INK4A immunohistochemistry staining for the progression of CIN grade 1 in China. Women with CIN1 histology were followed for two years. Prevalence of p16INK4A overexpression was found to increase with severity of malignant change, such that staining was observed in 75.5% and 79.6% of biopsies from women with CIN2 and CIN3, versus 42.7% for CIN1. Staining for p16INK4A was strongly associated with the presence of human papillomavirus.