P16、Ki67、PHH3及HPV-L1在宫颈癌及其癌前病变筛查中的意义

发布时间：2018-06-05 22:01

  本文选题：官颈癌 + 官颈脱落细胞　； 参考：《浙江大学》2014年硕士论文

【摘要】：背景： 宫颈癌是目前世界上女性最为常见的肿瘤之一,其发病率及相关死亡率均居女性恶性肿瘤的第二,但大多数宫颈癌及前驱病变中均可检出HPV,且由HPV感染到发展到宫颈癌的时间为3～15年时间不等。因此,常规进行宫颈癌筛查,采取合理治疗,能有效降低宫颈癌的发生率和死亡率。 当前,比较流行的宫颈癌筛查方式包括宫颈液基细胞学检测,与HPV-DNA检测。两者皆各有长处,而两者的结合,在一定程度上更能提高诊断的准确性,但是仍存在着特异性低、阳性预测值不理想等问题,寻找一些具有高灵敏度和高特异度的标志物来辅助诊断受到了广泛的关注,提高诊断的准确性,降低假阳性率和假阴性率,避免诊断失误,或过度治疗。 P16基因是近年来发现的与细胞周期调控密切相关的抑癌基因,可作为宫颈癌恶性程度的指标,为正确估计宫颈癌的预后、指导临床治疗提供依据。 Ki67蛋白是一种多克隆抗体,与细胞的有丝分裂密切相关,被认为是检测肿瘤细胞增殖活性最可靠指标之一。 PHH3(核分裂特异性抗体)可作为核分裂的特殊标记,快速、有效、客观地进行细胞增殖的定量分析。 HPV-L1蛋白是HPV的主要衣壳蛋白,是HPV感染复制早期的结构蛋白。通过检测HPV LI蛋白表达可以分析HPV感染的阶段。预测HPV感染后CIN的发展及预后,防止对某些宫颈癌前病变患者的过度治疗。 本文基于实验研究上述四个标志物在宫颈脱落细胞中的表达水平,探讨宫颈脱落细胞中,PHH3、P16、Ki67、HPV-L1的表达对宫颈病变筛查的意义。 目的： 检测P16、Ki67、PHH3以及HPV-L1在宫颈脱落细胞中的表达情况,评价其在细胞学诊断中的的价值,并与高危HPV DNA检测方法进行比较,以期提高宫颈癌及其癌前病变筛查的准确性。 方法： 选择浙江大学医学院附属妇产科医院2012年6月～2013年6月门诊同时行液基薄层细胞学(ThinPrepTM,Cytyccorp,Boxborough, Massachusetts,USA)检测和HPVHC-Ⅱ检测的患者120例,行阴道镜检查及组织病理学活检作为金标准,制成细胞蜡块,作P16、Ki67、PHH3、HPV-L1检测。 结果： 在120例患者中,P16的灵敏度为91.61%,特异度为85.42%,阳性预测值为90.41%,阴性预测值为87.23%；Ki67的灵敏度86.11%,特异度为91.67%,阳性预测值为93.94%,阴性预测值为81.48%；PHH3灵敏度为70.83%,特异度为100%,阳性预测值为100%,阴性预测值为69.57%。 110例宫颈脱落学检查异常的患者,经过HPV-DNA检测,均为阳性；以HPV-L1壳蛋白检测,显示在ASCUS/LSIL组病例中,HPV-L1的表达率为70%,在ASC-H/HSIL组病例中,HPV-L1的表达率为20%,在SCC组病例中,HPV-L1的表达率为O.ASCUS/LSIL中的HPV-L1壳蛋白阳性表达率远高于ASC-H/HSIL组以及SCC组,经统计学检测,P=0.007,具有统计学意义。 结论： 结合P16、Ki67、PHH3三个指标作免疫检查,可作为宫颈脱落细胞的一种辅助检查,提高ASC-H的检测准确性。HPV-L1可对ASCUS/LSIL患者进行有效分流。
[Abstract]:Background: cervical cancer is one of the most common tumors in women in the world. However, HPVs can be detected in most cervical cancer and precancerous lesions, and the time from HPV infection to cervical cancer development varies from 3 to 15 years. Therefore, conventional cervical cancer screening and rational treatment can effectively reduce the incidence and mortality of cervical cancer. At present, the more popular screening methods of cervical cancer include cervical liquid-based cytology, and HPV-DNA detection. Both have their own advantages, and the combination of the two can improve the accuracy of diagnosis to a certain extent, but there are still some problems such as low specificity, poor positive predictive value, etc. Finding some markers with high sensitivity and high heterogeneity to assist diagnosis has attracted wide attention, improving the accuracy of diagnosis, reducing false positive rate and false negative rate, and avoiding diagnostic errors. P16 gene is a tumor suppressor gene found in recent years, which is closely related to cell cycle regulation. P16 gene can be used as an indicator of the malignancy of cervical cancer and to correctly estimate the prognosis of cervical cancer. Ki67 protein is a polyclonal antibody that is closely related to cell mitosis. PHH3 (mitotic specific antibody) can be used as a special marker for mitosis, which can be used as a rapid, effective and objective quantitative analysis of cell proliferation. HPV-L1 protein is the main capsid protein of HPV. HPV infection is the early replication of structural proteins. The stage of HPV infection can be analyzed by detecting the expression of HPV Li protein. In order to predict the development and prognosis of cin after HPV infection and prevent over-treatment of some cervical precancerous lesions, the expression level of the above four markers in cervical exfoliated cells was studied experimentally. Objective: to investigate the significance of the expression of HPV-L1 in cervical exfoliated cells. Objective: to detect the expression of P16H3 and HPV-L1 in exfoliated cervical cells, and to evaluate their value in cytological diagnosis and compare with the methods of high risk HPV DNA detection. Methods: from June 2012 to June 2013, 120 patients with cervical cancer and their precancerous lesions were examined by ThinPrepTMTM CytyccorpBoxborough (Massachusetts USA) and HPVHC- 鈪，

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