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.
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。