|
|
|
| Value of combined detection of claudin 4 and high-risk human papilloma virus in high-grade squamous intraepithelial lesion and cervix squamous cell carcinoma |
DI Chenhong1( ),JIN Fan2,*() |
1. Department of Gynecology, Run Run Shaw International Medical Center, Hangzhou 310020, China
2. Department of Reproductive Genetics, Women's Hospital, Zhejiang University School of Medicine, Key Laboratory of Reproductive Genetics, Ministry of Education, Hangzhou 310006, China |
|
|
|
Abstract Objective: To investigate the expression of claudin 4 (CLDN4) in cervical tissues from patients with different cervical lesions, and to explore the value of combined detection of CLDN4 and high risk human papilloma virus (HR-HPV). Methods: The cervical tissue specimens of low-grade squamous intraepithelial lesion (LSIL, n=30), high-grade squamous intraepithelial lesion (HSIL, n=30), squamous cell carcinoma (SCC, n=30) as well as chronic cervicitis (control, n=30) were collected from the Sir Run Run Shaw Hospital of Zhejiang University during June 2015 and December 2016. The expression of CLDN4 protein in tissue specimens was detected by immunohistochemistry, HR-HPV was detected by real-time quantitative PCR, and the cervical exfoliated cells were examined by thinprep cytologic test (TCT). The ROC curve was applied to analyze the diagnostic value of TCT combined with HR-HPV and CLDN4 combined with HR-HPV tests for HSIL and SCC of the cervix. Results: With the increase of the severity of cervical lesions, the positive rate of CLDN4 expression rose (r=0.832, P < 0.05). Positivity of both HR-HPV infection and CLDN4 expression was found mainly in the HSIL and SCC groups. The areas under curve (AUC) of TCT combined with HR-HPV and CLDN4 combined with HR-HPV tests for diagnosis of HSIL and SCC were 0.683 and 0.633, respectively; the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of TCT combined with HR-HPV test for diagnosis of HSIL and SCC were 100.0%, 36.7%, 61.2%, 100.0% and 46.7% respectively; those of CLDN4 combined with HR-HPV test were 96.7%, 30.0%, 58.0%, 90.0% and 55.0%, respectively. Conclusions: CLDN4 expression may be related to the occurrence and development of cervical carcinoma and precancerous lesions. CLDN4 combined with HR-HPV test may be used for diagnosis of HSIL and SCC of the cervix clinically.
|
|
Received: 30 June 2018
Published: 04 December 2018
|
|
|
|
Corresponding Authors:
JIN Fan
E-mail: 296696990@qq.com;jinfan@zju.edu.cn
|
密封蛋白4与高危型人乳头瘤病毒联合检测对于高级别鳞状上皮内病变及宫颈鳞癌的诊断价值
目的: 探讨密封蛋白4（CLDN4）在不同级别宫颈病变组织中的表达及其与高危型人乳头瘤病毒（HR-HPV）联合检测的意义。方法: 选取2015年6月至2016年12月在浙江大学医学院附属邵逸夫医院妇科门诊就诊且经病理组织学检查证实的低级别鳞状上皮内病变（LSIL）、高级别鳞状上皮内病变（HSIL）和宫颈鳞癌患者的子宫颈组织标本各30份，同时选取30例慢性宫颈炎患者的子宫颈组织标本作为对照组。采用免疫组织化学法检测子宫颈组织中CLDN4蛋白表达，实时定量PCR检测HR-HPV，液基细胞学检查（TCT）检测宫颈脱落细胞学改变。采用ROC曲线分析比较TCT联合HR-HPV与CLDN4联合HR-HPV检测对HSIL和宫颈鳞癌的诊断价值。结果: 随着宫颈病变程度加重，CLDN4表达阳性率上升（r=0.832，P < 0.05）。HR-HPV感染与CLDN4表达共阳性主要出现在HSIL和宫颈癌组。TCT联合HR-HPV和CLDN4联合HR-HPV检测诊断HSIL和宫颈鳞癌的AUC分别为0.683和0.633。TCT联合HR-HPV检测诊断HSIL和宫颈鳞癌的敏感度、特异度、阳性预测值、阴性预测值和准确度分别为100.0%、36.7%、61.2%、100.0%、46.7%；CLDN4联合HR-HPV检测诊断HSIL和宫颈鳞癌的敏感度、特异度、阳性预测值、阴性预测值和准确度分别为96.7%、30.0%、58.0%、90.0%、55.0%。结论: CLDN4表达与宫颈鳞癌及癌前病变的发生和发展相关，CLDN4联合HR-HPV检测可指导临床HSIL及宫颈鳞癌的诊断和治疗。
关键词：
宫颈肿瘤/病理学,
宫颈肿瘤/诊断,
癌前状态/病理学,
癌前状态/诊断,
癌, 鳞状细胞/诊断,
乳头状瘤病毒科,
连接蛋白类/生物合成,
免疫组织化学
|
|
| [1] |
MOHANTY G , GHOSH S N . Risk factors for cancer of cervix, status of screening and methods for its detection[J]. Arch Gynecol Obstet, 2015, 291 (2): 247- 249
doi: 10.1007/s00404-014-3492-1
|
|
|
| [2] |
WANG B , HE M , CHAO A et al. Cervical cancer screening among adult women in China, 2010[J]. Oncologist, 2015, 20 (6): 627- 634
doi: 10.1634/theoncologist.2014-0303
|
|
|
| [3] |
温娜, 孟元光 . HPV E6/E7致病机制及在宫颈癌中研究进展[J]. 中国妇产科临床杂志, 2017, 18 (1): 92- 94
WEN Na , MENG Yuanguang . Research progress on pathogenesis of HPV E6/E7 in cervical cancer[J]. Chinese Journal of Clinical Obstetrics and Gynecology, 2017, 18 (1): 92- 94
|
|
|
| [4] |
王璐, 王晨阳, 王武亮 et al. 高危型人乳头瘤病毒E6/E7 mRNA检测对宫颈高度鳞状上皮内病变诊断及随访价值研究[J]. 中国实用妇科与产科杂志, 2016, 32 (6): 580- 582
WANG Lu , WANG Chenyang , WANG Wuliang et al. Clinical significance of high-risk HPV E6/E7 mRNA test in screening of HSIL+ and follow-up of HSIL-[J]. Chinese Journal of Practical Gynecology and Obstetrics, 2016, 32 (6): 580- 582
|
|
|
| [5] |
FIKS A G , GRUNDMEIER R W , MAYNE S et al. Effectiveness of decision support for families, clinicians, or both on HPV vaccine receipt[J]. Pediatrics, 2013, 131 (6): 1114- 1124
doi: 10.1542/peds.2012-3122
|
|
|
| [6] |
JOHNSTON E I , LOGANI S . Cytologic diagnosis of atypical squamous cells of undetermined significance in perimenopausal and postmenopausal women:lessons learned from human papillomavirus DNA testing[J]. Cancer, 2007, 111 (3): 160- 165
doi: 10.1002/cncr.22687
|
|
|
| [7] |
张玲, 袁良东.高危型人乳头瘤病毒E6 E7 mRNA检测筛检宫颈病变的临床价值[J/OL].世界最新医学信息文摘: 连续型电子期刊, 2015, 15(31): 140-140, 141.
ZHANG Ling, YUAN Liangdong. Clinical value of screening for cervical lesions by E6 E7 mRNA of high-risk human papillomavirus[J/OL]. World Latest Medicine Information, 2015, 15(31): 140-140, 141. (in Chinese)
|
|
|
| [8] |
加秋萍, 贺清波 . 评估TCT、HPV、c-MYC、hTERC基因联合检测在宫颈癌筛查中的应用价值[J]. 中国医师杂志, 2017, 19 (9): 1370- 1373, 1377
JIA Qiuping , HE Qingbo . Combined detection of TCT, HPV, c-MYC and hTERC genes in screening for cervical cancer[J]. Chinese Journal of Physicians, 2017, 19 (9): 1370- 1373, 1377
doi: 10.3760/cma.j.issn.1008-1372.2017.09.023
|
|
|
| [9] |
邹倩, 濮德敏, 周利平 et al. 液基超薄细胞技术及TBS系统检测2635例宫颈涂片的临床分析[J]. 中国实用妇科与产科杂志, 2006, 22 (4): 268- 270
ZOU Qian , PU Demin , ZHOU Liping et al. Clinical analysis of cervical smear using thinprep cytologic test and the Bethesda system[J]. Chinese Journal of Practical Gynecology and Obstetrics, 2006, 22 (4): 268- 270
doi: 10.3969/j.issn.1005-2216.2006.04.013
|
|
|
| [10] |
MORITA K , FURUSE M , FUJIMOTO K et al. Claudin multigene family encoding four-transmembrane domain protein components of tight junction strands[J]. Proc Natl Acad Sci U S A, 1999, 96 (2): 511- 516
doi: 10.1073/pnas.96.2.511
|
|
|
| [11] |
LECHPAMMER M , RESNICK M B , SABO E et al. The diagnostic and prognostic utility of claudin expression in renal cell neoplasms[J]. Mod Pathol, 2008, 21 (11): 1320- 1329
doi: 10.1038/modpathol.2008.116
|
|
|
| [12] |
ENGLISH D P , SANTIN A D . Claudins overexpression in ovarian cancer:potential targets for clostridium perfringens enterotoxin (CPE) based diagnosis and therapy[J]. Int J Mol Sci, 2013, 14 (5): 10412- 10437
doi: 10.3390/ijms140510412
|
|
|
| [13] |
NELH?BEL G A , KáROLY B , SZABó B et al. The prognostic role of claudins in head and neck squamous cell carcinomas[J]. Pathol Oncol Res, 2014, 20 (1): 99- 106
doi: 10.1007/s12253-013-9665-6
|
|
|
| [14] |
BENEVOLO M , VOCATURO A , CARACENI D et al. Sensitivity, specificity, and clinical value of human papillomavirus (HPV) E6/E7 mRNA assay as a triage test for cervical cytology and HPV DNA test[J]. J Clin Microbiol, 2011, 49 (7): 2643- 2650
doi: 10.1128/JCM.02570-10
|
|
|
| [15] |
LANDERS K A , SAMARATUNGA H , TENG L et al. Identification of claudin-4 as a marker highly overexpressed in both primary and metastatic prostate cancer[J]. Br J Cancer, 2008, 99 (3): 491- 501
doi: 10.1038/sj.bjc.6604486
|
|
|
| [16] |
BOIREAU S , BUCHERT M , SAMUEL M S et al. DNA-methylation-dependent alterations of claudin-4 expression in human bladder carcinoma[J]. Carcinogenesis, 2007, 28 (2): 246- 258
doi: 10.1093/carcin/bgl120
|
|
|
| [17] |
VINCE A , LEPEJ S Z . Diagnostic methods and techniques in cervical cancer prevention part Ⅱ:molecular diagnostics of HPV infection[J]. Med Glas(Zenica), 2010, 7 (1): 18- 25
|
|
|
| [18] |
WRIGHT T C , STOLER M H , BEHRENS C M et al. Primary cervical cancer screening with human papillomavirus:end of study results from the ATHENA study using HPV as the first-line screening test[J]. Gynecol Oncol, 2015, 136 (2): 189- 197
|
|
|
|
Viewed |
|
|
|
Full text
|
|
|
|
|
Abstract
|
|
|
|
|
Cited |
|
|
|
|
| |
Shared |
|
|
|
|
| |
Discussed |
|
|
|
|
