液基薄层细胞中HPV L1蛋白的表达在宫颈癌筛查中的意义
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摘要
目的:研究人乳头瘤病毒主要衣壳蛋白(HPV L1)在宫颈液基薄层细胞学(LPT)异常涂片中的表达,并结合组织病理学结果,探讨L1蛋白的表达与宫颈病变的关系,了解其能否作为辅助诊断指标用于宫颈癌的筛查中,为宫颈癌的早期诊断提供更加特异的方法。
方法:选择50例LPT检查结果为非典型鳞状上皮细胞(ASC-US)以上且hc2-HPV检测结果为阳性的LPT剩余标本及10例LPT正常且hc2-HPV阴性的标本,制作液基薄片,应用免疫细胞化学S-P法和非同位素标记核酸分子杂交技术,检测涂片中的L1蛋白,并与组织病理学结果进行对照。
结果:1.L1蛋白在对照组即NILM组的细胞涂片中无表达(0/10),在ASC-US、LSIL、HSIL组的阳性表达率分别为76.2%(16/21)、68.4%(13/19)、10%(1/10)。其中,ASC-US组及LSIL组的L1蛋白阳性率显著高于NILM组、HSIL组,差异有统计学意义,而HSIL组与NILM组,ASC-US组与LSIL组比较差异则无统计学意义。
2.与组织病理学诊断对照:10例对照组的病检结果皆为慢性炎症,余50例患者病检结果有慢性炎症、C1N-1、CIN-2、CIN-3、SCC,L1蛋白的阳性率分别为84.6%(11/13)、81.3%(13/16)、50.0%(5/10)、14.3%(1/7)、0.0%(0/4)。其中,CIN-2以上组有6例L1蛋白表达阳性(28.6%,6/21)。慢性炎症组及CIN-1组的L1蛋白阳性率显著高于对照组、CIN-2以上组,差异有统计学意义,而CIN-2以上组与对照组,慢性炎症组与CIN-1组的阳性率比较差异则无统计学意义。
结论:1.不同级别病变细胞中L1蛋白的表达存在明显差异,病变越重表达率越低。
2.L1蛋白不表达对宫颈高度病变具有一定的诊断价值,其可作为辅助诊断指标用于宫颈癌筛查中。
3.L1蛋白在一定程度上可反映HPV的感染状态。
4.LPT标本是很好的分子生物学的研究平台,适合进行免疫细胞化学分析和核酸分子杂交技术等多种实验性研究。将L1蛋白应用于LPT涂片上将有助于检出宫颈高度病变。
Objective:To research the expression of the key capsid protein of human papillomavirus(HPV L1) in abnormal liquid-based thiner cytology,at the same time, combine the results of biopsy histology to approach the relationship between L1 protein and cervical neoplasia.So that we can evaluate whether it can be used as a subsidiary diagnostic marker for cervical cancer screening and provide a more specific method for the early diagnosis of cervical carcinoma.
Methods:Selecting 50 patients whose LPT results were above atypical squamous cells of undetermined significance and hc2-HPV detect were positive,and 10 normal patients whose hc2-HPV detect were negative to make liqui-prep smears and to be done cervical biopsy under the colposcope.Using immunocytochemical streptaridin-peroxidase(S-P) method and non-isotope-labeled nucleic acid hybridization to test the L1 protein on 60 liqui-prep smears.At the same time, compared with the results of biopsy histology.
Results:1.L1 protein were no expression in the control group.In patients with cytological diagnosis of atypical squamous cells of undetermined significance (ASC-US),low grade squamous intraepithelial lesion(LSIL),and high grade squamous intraepithelial lesion(HSIL),the positive rates of L1 protein were 76.2%(16/21),68.4%(13/19),10%(1/10),respectively.The positive rate in ASC-US or LSIL was significantly higher than NILM,HSIL,but unmarked difference bteween the other group.
2.Compared with the results of biopsy histology,the control group pathologic result were chronic inflammation.The pathologic diagnosis results of remaining 50 patients were chronic inflammation,CIN-1,CIN-2,CIN-3 and SCC,which's positive rates of L1 protein were 84.6%(11/13),81.3%(13/16),50.0%(5/10),14.3%(1/7), 0.0%(0/4),respectively.The positive rate of the groups above CIN-2 was 28.6%(6/21). The positive rate in chronic inflammation or C1N-1 was significantly higher than the control group,and the groups above CIN-2,but unmarked difference bteween the other group.
Conclusion:1.The expression rates of L1 protein were significantly different in different cytopathology diagnosis,the more severe lesions,the lower expression rates.
2.L1 protein-negative has some diagnostic value to high level cervical lesions, which can be used as a subsidiary diagnostic marker for cervical cancer screening.
3.L1 protein reflect the status of HPV infection in a certain extent.
4.Liqui-prep samples adapt to do immunocytochemical analysis and nucleic acid hybridization.We believe it supplies a useful plat to research the variety biomolecules of cervical lesion.Using L1 protein in LPT smear will help our clinical doctors to find out high level cervical lesions.
方法:选择50例LPT检查结果为非典型鳞状上皮细胞(ASC-US)以上且hc2-HPV检测结果为阳性的LPT剩余标本及10例LPT正常且hc2-HPV阴性的标本,制作液基薄片,应用免疫细胞化学S-P法和非同位素标记核酸分子杂交技术,检测涂片中的L1蛋白,并与组织病理学结果进行对照。
结果:1.L1蛋白在对照组即NILM组的细胞涂片中无表达(0/10),在ASC-US、LSIL、HSIL组的阳性表达率分别为76.2%(16/21)、68.4%(13/19)、10%(1/10)。其中,ASC-US组及LSIL组的L1蛋白阳性率显著高于NILM组、HSIL组,差异有统计学意义,而HSIL组与NILM组,ASC-US组与LSIL组比较差异则无统计学意义。
2.与组织病理学诊断对照:10例对照组的病检结果皆为慢性炎症,余50例患者病检结果有慢性炎症、C1N-1、CIN-2、CIN-3、SCC,L1蛋白的阳性率分别为84.6%(11/13)、81.3%(13/16)、50.0%(5/10)、14.3%(1/7)、0.0%(0/4)。其中,CIN-2以上组有6例L1蛋白表达阳性(28.6%,6/21)。慢性炎症组及CIN-1组的L1蛋白阳性率显著高于对照组、CIN-2以上组,差异有统计学意义,而CIN-2以上组与对照组,慢性炎症组与CIN-1组的阳性率比较差异则无统计学意义。
结论:1.不同级别病变细胞中L1蛋白的表达存在明显差异,病变越重表达率越低。
2.L1蛋白不表达对宫颈高度病变具有一定的诊断价值,其可作为辅助诊断指标用于宫颈癌筛查中。
3.L1蛋白在一定程度上可反映HPV的感染状态。
4.LPT标本是很好的分子生物学的研究平台,适合进行免疫细胞化学分析和核酸分子杂交技术等多种实验性研究。将L1蛋白应用于LPT涂片上将有助于检出宫颈高度病变。
Objective:To research the expression of the key capsid protein of human papillomavirus(HPV L1) in abnormal liquid-based thiner cytology,at the same time, combine the results of biopsy histology to approach the relationship between L1 protein and cervical neoplasia.So that we can evaluate whether it can be used as a subsidiary diagnostic marker for cervical cancer screening and provide a more specific method for the early diagnosis of cervical carcinoma.
Methods:Selecting 50 patients whose LPT results were above atypical squamous cells of undetermined significance and hc2-HPV detect were positive,and 10 normal patients whose hc2-HPV detect were negative to make liqui-prep smears and to be done cervical biopsy under the colposcope.Using immunocytochemical streptaridin-peroxidase(S-P) method and non-isotope-labeled nucleic acid hybridization to test the L1 protein on 60 liqui-prep smears.At the same time, compared with the results of biopsy histology.
Results:1.L1 protein were no expression in the control group.In patients with cytological diagnosis of atypical squamous cells of undetermined significance (ASC-US),low grade squamous intraepithelial lesion(LSIL),and high grade squamous intraepithelial lesion(HSIL),the positive rates of L1 protein were 76.2%(16/21),68.4%(13/19),10%(1/10),respectively.The positive rate in ASC-US or LSIL was significantly higher than NILM,HSIL,but unmarked difference bteween the other group.
2.Compared with the results of biopsy histology,the control group pathologic result were chronic inflammation.The pathologic diagnosis results of remaining 50 patients were chronic inflammation,CIN-1,CIN-2,CIN-3 and SCC,which's positive rates of L1 protein were 84.6%(11/13),81.3%(13/16),50.0%(5/10),14.3%(1/7), 0.0%(0/4),respectively.The positive rate of the groups above CIN-2 was 28.6%(6/21). The positive rate in chronic inflammation or C1N-1 was significantly higher than the control group,and the groups above CIN-2,but unmarked difference bteween the other group.
Conclusion:1.The expression rates of L1 protein were significantly different in different cytopathology diagnosis,the more severe lesions,the lower expression rates.
2.L1 protein-negative has some diagnostic value to high level cervical lesions, which can be used as a subsidiary diagnostic marker for cervical cancer screening.
3.L1 protein reflect the status of HPV infection in a certain extent.
4.Liqui-prep samples adapt to do immunocytochemical analysis and nucleic acid hybridization.We believe it supplies a useful plat to research the variety biomolecules of cervical lesion.Using L1 protein in LPT smear will help our clinical doctors to find out high level cervical lesions.
引文
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[2]Parkin DM,Bray F,Ferlay J,et al.Estimating the world cancer burden:Globocan 2000.Int J Cancer,2001,94(2):153-156
[3]Schlecht NF,Trevisan S,Duarte-Franco E,et al.Viral load as a predictor of the risk of cervical intraepithelial neoplasia.Int J Cancer,2003,103(4):519-524
[4]岑坚敏,钱德英,黄志宏,等.阴道镜对宫颈上皮内瘤变的诊断价值.中国实用妇科与产科杂志,2003,19(4):215
[5]岑坚敏,钱德英,曾仁海,等.高危型人乳头瘤病毒负荷量与宫颈癌及癌前病变的相关性研究.中国实用妇科与产科杂志,2007,23(7):533-535
[6]Agnantis NJ,Sotiriadis A,Paraskevaidis E.The current status of HPV DNA testing.Eur J Gynaecol Oncol,2003,24(5):351-356
[7]Hesselink AT,van den Brule AJ,Brink AA,et al.Comparison of hybrid capture 2 with in situ hybridization for the detection of high-risk human papillomavirus in liquid-based cervical samples.Cancer,2004,102(1):11-18
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