人乳头瘤病毒E6/E7、人端粒酶逆转录酶（hTERT）和Ki67 mRNA逆转录定量聚合酶链反应（RT-qPCR）检测对宫颈癌女性福尔马林固定石蜡包埋宫颈组织标本的诊断效能
Diagnostic performance of HPV E6/E7, hTERT, and Ki67 mRNA RT-qPCR assays on formalin-fixed paraffin-embedded cervical tissue specimens from women with cervical cancer.
作者信息
Wang Hye-Young, Kim Geehyuk, Cho Hyemi, Kim Sunghyun, Lee Dongsup, Park Sunyoung, Park Kwang Hwa, Lee Hyeyoung
机构信息
M&D, Inc., Wonju Eco Environmental Technology Center, Wonju, Gangwon, Republic of Korea.
Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University, Wonju, Gangwon, Republic of Korea.
出版信息
Exp Mol Pathol. 2015 Jun;98(3):510-6. doi: 10.1016/j.yexmp.2015.03.036. Epub 2015 Mar 31.
Human papillomavirus (HPV) is a major cause of cervical cancer, which is the third most common cancer in women. Human telomerase reverse transcriptase (hTERT) and Ki67 are tumor cell markers indicating cancer cell proliferation in cancer patients, and activation of hTERT and Ki67 leads to progressive cervical carcinogenesis. In the present study, we evaluated the CervicGen HPVE6/E7 mRNA RT-qDx assay, which detects 16 HPV high-risk (HR) genotypes (HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68 and 69), and the CervicGen hTERT and Ki67 mRNA RT-qDx assay using 117 formalin-fixed paraffin-embedded (FFPE) cervical cancer tissue samples. The diagnostic validity of the CervicGen HPV RT-qDx assay for detecting histologically proven prevalent squamous cell carcinoma (SCC) was 94% sensitivity, 100% specificity, 77.8% positive predictive value (PPV), and 78.9% negative predictive value (NPV). The most common HPV genotypes detected in FFPE cervical cancer tissue samples were HPV 16 (56%) and HPV 18 (10%). The positivity rate of hTERT and Ki67 mRNA expressions in FFPE cervical cancer tissue samples on RT-qPCR was 65% and 93% respectively. Moreover, the positivity rates were 92% for a combination of HPV E6/E7 and hTERT mRNA expressions, 97% for HPV E6/E7 and Ki67 mRNA expressions, and 99% (99/100) for the combination of HPV E6/E7, hTERT, and Ki67 mRNA expressions. These data showed that SSC FFPE cervical cancer tissue samples correlated more strongly with high Ki67 mRNA expressions than with hTERT mRNA expressions. Notably, hTERT and Ki67 mRNA expression level was increased in high-grade cervical lesions, but was very low in normal samples. Our findings suggest that the combination of HPV E6/E7, hTERT, and Ki67 mRNA expression levels could be used in a complementary manner in diagnosing high-grade cervical lesions. Further studies are required to evaluate these assays as a useful predictive tool for screening low-grade cervical lesions.
人乳头瘤病毒（HPV）是宫颈癌的主要病因，宫颈癌是女性中第三大常见癌症。人端粒酶逆转录酶（hTERT）和Ki67是肿瘤细胞标志物，表明癌症患者体内癌细胞的增殖，hTERT和Ki67的激活会导致宫颈癌的逐步发生。在本研究中，我们评估了CervicGen HPVE6/E7 mRNA RT-qDx检测法，该方法可检测16种HPV高危（HR）基因型（HPV 16、18、31、33、35、39、45、51、52、53、56、58、59、66、68和69），以及使用117份福尔马林固定石蜡包埋（FFPE）宫颈癌组织样本的CervicGen hTERT和Ki67 mRNA RT-qDx检测法。CervicGen HPV RT-qDx检测法对经组织学证实的常见鳞状细胞癌（SCC）的诊断有效性为：灵敏度94%、特异性100%、阳性预测值（PPV）77.8%、阴性预测值（NPV）78.9%。在FFPE宫颈癌组织样本中检测到的最常见HPV基因型为HPV 16（56%）和HPV 18（10%）。RT-qPCR检测FFPE宫颈癌组织样本中hTERT和Ki67 mRNA表达的阳性率分别为65%和93%。此外，HPV E6/E7和hTERT mRNA表达组合的阳性率为92%，HPV E6/E7和Ki67 mRNA表达组合的阳性率为97%，HPV E6/E7、hTERT和Ki67 mRNA表达组合的阳性率为99%（99/100）。这些数据表明，SSC FFPE宫颈癌组织样本与高Ki67 mRNA表达的相关性比与hTERT mRNA表达的相关性更强。值得注意的是，hTERT和Ki67 mRNA表达水平在高级别宫颈病变中升高，但在正常样本中非常低。我们的研究结果表明，HPV E6/E7、hTERT和Ki67 mRNA表达水平的组合可在诊断高级别宫颈病变时以互补方式使用。需要进一步研究以评估这些检测法作为筛查低级别宫颈病变的有用预测工具。
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