HTERC基因在宫颈上皮内瘤样病变治疗后监测的相关性研究

doi:10.3969/j.issn.1006-7795.2015.06.020

摘要/Abstract

摘要： 目的探讨人端粒酶RNA 基因(human telomerase RNA component,HTERC)在宫颈上皮内瘤样病变(cervical intraepithelial neapalsia,CIN)治疗后病情监测中的价值。方法选取83例CIN患者,治疗前均行宫颈脱落细胞学检查(thin prep cytologic test,TCT)、高危型人乳头瘤病毒(high risk-human papillomavirus,HR-HPV)、阴道镜活检及HTERC检测。于治疗后6个月及1年随访时再次行上述检查。结果 1 随宫颈病变程度增加,HTERC基因阳性表达率增加,且差异有统计学意义;2 治疗后半年复查发现细胞学异常程度、高危型HPV阳性率及HTERC基因检测阳性率较治疗前均有显著减少,差异具有统计学意义;但HTERC阳性患者较HTERC阴性患者治疗后相比,宫颈病变转归差异无统计学意义;3 几种检测方法比较,宫颈脱落细胞学检查对于宫颈病变的阳性预测值相对较强,HR-HPV检查对于宫颈病变预测的灵敏度和阴性预测值相对较高,HTERC检测对于宫颈病变预测特异度最高。结论在患者有HR-HPV持续感染、特别是宫颈出现CIN改变时,可行HTERC基因检测辅助预测病变的发展情况。

关键词: 人端粒酶RNA基因, 宫颈上皮内瘤样病变, 原位荧光杂交技术, 人乳头瘤病毒, 宫颈脱落细胞学检查

Abstract: Objective To explore the monitoring value of human telomerase RNA component(HTERC) gene in cervical intraepithelial neapalsia(CIN) after the treatment. Methods Totally eight-three patients confirmed as cervical intraepithelial neapalsia were chosen. Those patients were examined with thin prep cytologic test(TCT), high risk-human papillomavirus(HR-HPV) detection, multi-point biopsy and HTERC gene preoperative. Then we examined TCT, HPV, HTERC gene and colposcopy biopsy at the time of 6 months and 1 year follow-up. Results 1 With the histological lesion degree increasing, HTERC gene positive expression rate increased, and the increased difference is statistically significant. 2 Half year after the treatment, we discovered that the cytology, high-risk type HPV positive rate and positive HTERC gene detection rate(HTERC gene positive rate was 0% after the treatment), were significantly reduced compared with preoperative, and it suggested that the surgery could effectively reduce the degree of cervical lesions, high-risk type HPV positive rate and positive rate of HTERC gene. 3 Comparing those tests, we found that the TCT had the highest positive predictive value, the HR-HPV had the highest sensitivity and negative predictive value, and the HTERC had the highest specificity. Conclusion When patients have HR-HPV infection, and especially have the CIN, it will help predict the direction of development of the disease with the HTERC gene detects added.

Key words: human telomerase RNA component, cervical intraepithelial neapalsia, fluorescence in situ hybridizatiom, human papillomavirus, thin prep cytologic test

中图分类号:

周丽红, 贺昕红, 龙燕, 蔺莉. HTERC基因在宫颈上皮内瘤样病变治疗后监测的相关性研究[J]. 首都医科大学学报, 2015, 36(6): 946-952.

Zhou Lihong, He Xihong, Long Yan, Lin Li. Related research of HTERC gene in cervical intraepithelial neapalsia after the treatment[J]. Journal of Capital Medical University, 2015, 36(6): 946-952.

参考文献

[1] Cox J T, Castle P E, Behrens C M, et al. Comparison of cervical cancer screening strategies incorporating different combinations of cytology, HPV testing, and genotyping for HPV 16/18: results from the ATHENA HPV study[J]. Am J Obstet Gynecol, 2013,208(3):184 e181-184 e111.
[2] Ronco G, Dillner J, Elfström K. M, et al. Efficacy of HPV-based screening for prevention of invasive cervical cancer: follow-up of four European randomised controlled trials[J]. Lancet, 2014,383(9916):524-532.
[3] 李秋霞,张玉英,石青岭,等.巴氏涂片与液基细胞学(TCT)宫颈检查结果分析[J].中国现代药物应用,2010,4(9):95-96.
[4] 潘虹,陈丽艳.高危型人乳头瘤病毒HC2检测在宫颈上皮内瘤变筛查中的意义[J].肿瘤预防与治疗,2011,24(6):332-334.
[5] 杨维娜,尹利荣,段青,等.宫颈上皮内瘤变治疗前后hTERC基因表达结果分析[J].天津医药,2010,38(8):654-665.
[6] Zhen S, Hu C M, Bian L H. Glutathione S-transferase polymorphism interactions with smoking status and HPV infection in cervical cancer risk: an evidence-based meta-analysis[J]. PloS one, 2013,8(12):e83497.
[7] Pileggi C, Flotta D, Bianco A, et al. Is HPV DNA testing specificity comparable to that of cytological testing in primary cervical cancer screening? Results of a meta-analysis of randomized controlled trials[J]. Int J Cancer, 2014,135(1):166-177.
[8] 刘冠军,吴冬梅,程慧欣.宫颈传统脱落细胞学结果与患者年龄及临床诊断相关性分析[J].中国煤炭工业医学杂志,2012,15(12):1835-1838.
[9] 黄宝英,周伦顺,富显果,等.HPV 1/E7 mRNA检测对宫颈癌筛查意义的初步评价[J].中华肿瘤防治杂志,2013,20(14):1061-1064.
[10] Li T, Tang L, Bian D, et al. Detection of hTERC and c-MYC genes in cervical epithelial exfoliated cells for cervical cancer screening[J]. Int J Mol Med, 2014,33(5):1289-1297.
[11] Bin H, Ruifang W, Ruizhen L, et al. Detention of HPV L1 capsid protein and hTERC gene in screening of cervical cancer[J]. Iran J Basic Med Sci, 2013,16(6):797-802.
[12] He C, Xu C, Xu M, et al. Genomic amplification of hTERC in paraffin-embedded tissues of cervical intraepithelial neoplasia and invasive cancer[J]. Int J Gynecol Pathol, 2012,31(3):280-285.
[13] Chen M, Xing L N. siRNA-mediated inhibition of hTERC enhances radiosensitivity of cervical cancer[J]. Asian Pac J Cancer Prev, 2012,13(12):5975-5979.
[14] Hopman A H, Theelen W, Hommelberg P P, et al. Genomic integration of oncogenic HPV and gain of the human telomerase gene TERC at 3q26 are strongly associated events in the progression of uterine cervical dysplasia to invasive cancer[J]. J Pathol, 2006,210(4):412-419.
[15] Andersson S, Sowjanya P, Wangsa D, et al. Detection of genomic amplification of the human telomerase gene TERC, a potential marker for triage of women with HPV-positive, abnormal Pap smears[J]. Am J Pathol, 2009,175(5):1831-1847.
[16] Tu Z, Zhang A, Wu R, et al. Genomic amplification of the human telomerase RNA gene for differential diagnosis of cervical disorders[J]. Cancer Genet Cytogenet, 2009,191(1):10-16.
[17] Heselmeyer-Haddad K, Sommerfeld K, White N M, et al. Genomic amplification of the human telomerase gene(TERC) in pap smears predicts the development of cervical cancer[J]. Am J Pathol, 2005,166(4):1229-1238.
[18] Alameda F, Espinet B, Corzo C, et al. 3q26(hTERC) gain studied by fluorescence in situ hybridization as a persistence-progression indicator in low-grade squamous intraepithelial lesion cases[J]. Hum Pathol, 2009,40(10):1474-1478.
[19] Ciavattini A, Stortoni P, Mancioli F, et al. The impact of loop electrosurgical excision procedure(LEEP) for CIN 2, 3 on spontaneous preterm delivery in twin pregnancies by assisted reproductive technique: preliminary data[J]. J Matern Fetal Neonatal Med, 2014,27(11):1169-1171.
[20] Duesing N, Schwarz J, Choschzick M, et al. Assessment of cervical intraepithelial neoplasia(CIN) with colposcopic biopsy and efficacy of loop electrosurgical excision procedure(LEEP)[J]. Arch Gynecol Obstet, 2012,286(6):1549-1554.
[21] Singh A, Arthur B, Agarwal V. LEEP verses cryotherapy in CIN[J]. J Obstet Gynaecol India, 2011,61(4):431-435.
[22] Chen S, Yang Z, Zhang Y, et al. Genomic amplification patterns of human telomerase RNA gene and C-MYC in liquid-based cytological specimens used for the detection of high-grade cervical intraepithelial neoplasia[J]. Diagn Pathol, 2012,7:40.
[23] 常小垒,郭科军,张颐.HPV亚型与子宫颈癌前病变及癌变的关系探讨[J].中国医科大学学报,2014,43(8):720-723,727.