人乳头瘤病毒E6/E7 mRNA及p16/Ki-67蛋白共表达在不同级别宫颈病变中的临床意义
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摘要
目的:探讨人乳头瘤病毒E6/E7 mRNA及p16/Ki-67蛋白在不同级别宫颈病变中的表达情况。方法:收集在郑州大学第二附属医院妇科门诊就诊的妇女537例,采用APTIMA human papillomavirus(HPV)实验和CINtec PLUS技术分别检测E6/E7 mRNA及p16/Ki-67蛋白,所有妇女均行阴道镜活检和病理学检查。结果:537例妇女的平均年龄为43.88±10.97岁。HPV mRNA和p16/Ki-67阳性率均随着病理诊断级别的升高而增加(P<0.001),HPV mRNA和p16/Ki-67在病理正常人群中的阳性率分别为19.1%和13.1%,在宫颈鳞癌(squamous cell carcinoma,SCC)中的阳性率分别为100.0%和97.7%。与在不同病理级别中的阳性率趋势基本一致,HPV mRNA与p16/Ki-67的阳性率也随着细胞学结果的严重程度增加而升高(P<0.001)。HPV mRNA和p16/Ki-67在细胞学正常人群中的阳性率分别为18.6%和14.2%,在宫颈SCC中的阳性率分别为100.0%和93.5%。结论:HPV mRNA与p16/Ki-67蛋白共表达与宫颈病变程度呈正相关,或可通过监测患者HPV mRNA和p16/Ki-67表达水平有效评估宫颈病变状况。
Objective: To explore the clinical significance of human papillomavirus(HPV) E6/E7 mRNA and p16/Ki-67 protein in different phases of cervical lesions. Methods: A total of 537 women were enrolled in the Second Affiliated Hospital of Zhengzhou University. E6/E7 mRNA and p16/Ki-67 were detected by APTIMA HPV assay and CINtec PLUS technology, respectively. All admitted women underwent colposcopy biopsy and pathological examination. Results: The mean age of 537 women was 43.88±10.97. The positive rates of HPV mRNA and p16/Ki-67 increased as pathologic diagnosis progressed(P<0.001). For normal people, the positive rates of HPV mRNA and p16/Ki-67 were 19.1% and 13.1%, respectively. As for those with squamous cell carcinoma(SCC) of the cervix, the positive rates were 100.0% and 97.7%, respectively. The positive rates of HPV mRNA and p16/Ki-67 also increased as cytological results worsened(P<0.001). The positive rates of HPV mRNA and p16/Ki-67 were 18.6% and 14.2% in the normal group, and those in the SCC of the cervix group were 100% and 93.5%, respectively. Conclusion: The expression of HPV mRNA and p16/Ki-67 protein are positively correlated with cervical lesions. The condition of cervical lesions can be effectively assessed by monitoring the expression level of HPV mRNA and p16/Ki-67 protein.
Objective: To explore the clinical significance of human papillomavirus(HPV) E6/E7 mRNA and p16/Ki-67 protein in different phases of cervical lesions. Methods: A total of 537 women were enrolled in the Second Affiliated Hospital of Zhengzhou University. E6/E7 mRNA and p16/Ki-67 were detected by APTIMA HPV assay and CINtec PLUS technology, respectively. All admitted women underwent colposcopy biopsy and pathological examination. Results: The mean age of 537 women was 43.88±10.97. The positive rates of HPV mRNA and p16/Ki-67 increased as pathologic diagnosis progressed(P<0.001). For normal people, the positive rates of HPV mRNA and p16/Ki-67 were 19.1% and 13.1%, respectively. As for those with squamous cell carcinoma(SCC) of the cervix, the positive rates were 100.0% and 97.7%, respectively. The positive rates of HPV mRNA and p16/Ki-67 also increased as cytological results worsened(P<0.001). The positive rates of HPV mRNA and p16/Ki-67 were 18.6% and 14.2% in the normal group, and those in the SCC of the cervix group were 100% and 93.5%, respectively. Conclusion: The expression of HPV mRNA and p16/Ki-67 protein are positively correlated with cervical lesions. The condition of cervical lesions can be effectively assessed by monitoring the expression level of HPV mRNA and p16/Ki-67 protein.
引文
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[6] 王海瑞, 廖光东, 陈汶, 等. p16/Ki-67免疫细胞化学双染在宫颈癌筛查中的应用价值[J]. 中华肿瘤杂志, 2017, 39(8):636-640.
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[10] Arnold-Jan K,Susanne B,Janssen EA,et al. The relationship between syntactic structure analysis features,histological grade and high--risk HPV DNA in cervical intraepithelial neoplasia[J].Cell Oncol, 2016, 26(3): 135-141.
[11] Burger EA, Korn?r H, Klemp M, et al. HPV mRNA tests for the detection of cervical intraepithelial neoplasia: a systematic review [J]. Gynecol Oncol, 2011, 120(3): 430-438.
[12] Tommasino M. The human papillomavirus family and its role in carcinogenesis [J]. Semin Cancer Biol, 2014, 26:13-21.
[13] Vinokurova S, Wentzensen N, Kraus I, et al. Type-dependent integration frequency of human papillomavirus genomes in cervical lesions [J]. Cancer Res, 2008, 68(1):307-313.
[14] Hang D, Gao L, Sun M, et al. Functional effects of sequence variations in the E6 and E2 genes of human papillomavirus 16 European and Asian variants [J]. J Med Virol, 2014, 86(4):618-626.
[15] Ruttkay-Nedecky B, Jimenez Jimenez AM, Nejdl L, et al. Relevance of infection with human papillomavirus: the role of the p53 tumor suppressor protein and E6/E7 zinc finger proteins [J]. Int J Oncol, 2013, 43(6):1754-1762.
[16] Longworth MS, Laimins LA. Pathogenesis of human papillomaviruses in differentiating epithelia [J]. Microbiol Mol Biol Rev, 2004, 68(2): 362-372.
[17] 李晓林,袁文娟,陈龙,等. 高危型HPV E6/E7 mRNA检测在宫颈机会性筛查中应用价值研究[J].中华肿瘤防治杂志, 2017, 24 (4):217-222。
[18] Duvlis S, Popovska-Jankovic K, Arsova ZS, et al. HPV E6/E7 mRNA versus HPV DNA biomarker in cervical cancer screening of a group of Macedonian women[J]. J Med Virol, 2015, 87(9): 1578-1586.
[19] Ratnam S, Coutlee F, Fontaine D, et al. Clinical performance of the PreTect HPV-proofer E6/E7 mRNA assay in comparison with that of the hybrid capture 2 test for identification of women at risk of cervical cancer [J]. J Clin Microbiol, 2010, 48(8): 2779-2785.
[20] Klaes R, Friedrich T, Spitkovsky D, et al. Overexpression of p16 (INK4A) as specific marker for dysplastic and neoplastic epithelial cells of the cervix uteri [J]. Int J Cancer, 2001, 92(2):276-284.
[21] Heatley MK. Ki67 protein: the immaculate deception? [J]. Histopathology, 2002, 40(5):483.
[22] Yu LL,Chen W, Lei XQ, et al. Evaluation of p16/Ki-67 dual staining in detection of cervical precancer and cancers: a multicenter study in China [J]. Oncotarget, 2016, 7(16): 21181-21189.
[23] Wentzensen N, Schwartz L, Zuna RE, et al. Performance of p16/Ki-67 immunostaining to detect cervical cancer precursors in colposcopy referral population [J]. Clin Cancer Res, 2012, 18(15):4154-4162.
[24] 张睿怡, 郭红燕, 游珂, 等. p16INK4a/Ki67免疫细胞化学双染在检出宫颈癌及癌前病变中的作用[J]. 肿瘤预防与治疗, 2017, 30(6): 427-432.
[2] Bosch FX, Lorincz A, Muňoz N, et al. The causal relation between human papillomavirus and cervical cancer [J]. J Clin Pathol, 2002, 55(4):244-265.
[3] Schlecht NF, Kulaga S, Robitaille J, et al. Persistent human papillomavirus infection as a predictor of cervical intraepithelial neoplasia [J]. JAMA, 2001, 286(24): 3106-3114.
[4] Castle PE, Wacholder S, Lorincz AT, et al. A prospective study of high-grade cervical neoplasia risk among human papillomavirus-infected women [J]. J Natl Cancer Inst, 2002, 94(18):1406-1414.
[5] Wentzensen N, von Knebel DM. Biomarkers in cervical cancer screening[J]. Dis Markers, 2007, 23(4):315-330.
[6] 王海瑞, 廖光东, 陈汶, 等. p16/Ki-67免疫细胞化学双染在宫颈癌筛查中的应用价值[J]. 中华肿瘤杂志, 2017, 39(8):636-640.
[7] Brisson M,Drolet M,Bénard E,et al. Effect of HPV on cervical cancer screening in Alberta [J]. CMAJ, 2016, 188(14): 1035.
[8] Moyer VA. Preventive Services Task Force. Screening for cervical cancer: U. S. Preventive Services Task Force recommendation statement [J]. Ann Intern Med, 2012, 156(12):880-891.
[9] Saslow D, Solomon D, Lawson HW, et al. American Cancer Society, American Society for Colposcopy and Cervical Pathology, and American Society for Clinical Pathology screening guidelines for the prevention and early detection of cervical cancer[J]. CA Cancer J Clin, 2012, 62(3): 147-172.
[10] Arnold-Jan K,Susanne B,Janssen EA,et al. The relationship between syntactic structure analysis features,histological grade and high--risk HPV DNA in cervical intraepithelial neoplasia[J].Cell Oncol, 2016, 26(3): 135-141.
[11] Burger EA, Korn?r H, Klemp M, et al. HPV mRNA tests for the detection of cervical intraepithelial neoplasia: a systematic review [J]. Gynecol Oncol, 2011, 120(3): 430-438.
[12] Tommasino M. The human papillomavirus family and its role in carcinogenesis [J]. Semin Cancer Biol, 2014, 26:13-21.
[13] Vinokurova S, Wentzensen N, Kraus I, et al. Type-dependent integration frequency of human papillomavirus genomes in cervical lesions [J]. Cancer Res, 2008, 68(1):307-313.
[14] Hang D, Gao L, Sun M, et al. Functional effects of sequence variations in the E6 and E2 genes of human papillomavirus 16 European and Asian variants [J]. J Med Virol, 2014, 86(4):618-626.
[15] Ruttkay-Nedecky B, Jimenez Jimenez AM, Nejdl L, et al. Relevance of infection with human papillomavirus: the role of the p53 tumor suppressor protein and E6/E7 zinc finger proteins [J]. Int J Oncol, 2013, 43(6):1754-1762.
[16] Longworth MS, Laimins LA. Pathogenesis of human papillomaviruses in differentiating epithelia [J]. Microbiol Mol Biol Rev, 2004, 68(2): 362-372.
[17] 李晓林,袁文娟,陈龙,等. 高危型HPV E6/E7 mRNA检测在宫颈机会性筛查中应用价值研究[J].中华肿瘤防治杂志, 2017, 24 (4):217-222。
[18] Duvlis S, Popovska-Jankovic K, Arsova ZS, et al. HPV E6/E7 mRNA versus HPV DNA biomarker in cervical cancer screening of a group of Macedonian women[J]. J Med Virol, 2015, 87(9): 1578-1586.
[19] Ratnam S, Coutlee F, Fontaine D, et al. Clinical performance of the PreTect HPV-proofer E6/E7 mRNA assay in comparison with that of the hybrid capture 2 test for identification of women at risk of cervical cancer [J]. J Clin Microbiol, 2010, 48(8): 2779-2785.
[20] Klaes R, Friedrich T, Spitkovsky D, et al. Overexpression of p16 (INK4A) as specific marker for dysplastic and neoplastic epithelial cells of the cervix uteri [J]. Int J Cancer, 2001, 92(2):276-284.
[21] Heatley MK. Ki67 protein: the immaculate deception? [J]. Histopathology, 2002, 40(5):483.
[22] Yu LL,Chen W, Lei XQ, et al. Evaluation of p16/Ki-67 dual staining in detection of cervical precancer and cancers: a multicenter study in China [J]. Oncotarget, 2016, 7(16): 21181-21189.
[23] Wentzensen N, Schwartz L, Zuna RE, et al. Performance of p16/Ki-67 immunostaining to detect cervical cancer precursors in colposcopy referral population [J]. Clin Cancer Res, 2012, 18(15):4154-4162.
[24] 张睿怡, 郭红燕, 游珂, 等. p16INK4a/Ki67免疫细胞化学双染在检出宫颈癌及癌前病变中的作用[J]. 肿瘤预防与治疗, 2017, 30(6): 427-432.