宫颈组织中增殖细胞抗原和微血管密度的表达及相关性分析

Expression and correlation analysis of proliferating cell antigen and microvessel density in cervical tissue

目的研究增殖细胞抗原(PCNA)和微血管密度(MVD)在宫颈组织中的表达特点,探讨二者联合应用的诊断价值。方法选取2018年12月—2020年12月在杭州市第三人民医院行宫颈液基薄层细胞学检查和高危型人乳头瘤病毒(HPV)检测的患者为研究对象,根据国际癌症协会对宫颈/阴道细胞学的诊断标准,对宫颈液基薄层细胞学筛查异常或筛查正常且HPV16或18阳性的患者行阴道镜下宫颈组织活检,经病理诊断证实为宫颈上皮内瘤变(CIN)行宫颈环形电切除术或宫颈冷刀锥切术的患者63例为观察组,其中CINⅠ级28例,CINⅡ/Ⅲ级35例,另选取同期在该院因子宫肌瘤行子宫切除术,同时病理诊断为正常宫颈组织的患者25例作为对照组。对所有患者的石蜡标本进行观察,取病变最严重区域行PCNA和MVD免疫组化染色。结果对照组PCNA的阳性表达率为64.00%;CINⅠ级组PCNA的阳性表达率为96.43%;CINⅡ/Ⅲ级组中PCNA的阳性表达率为100.00%。对照组PCNA阳性过表达率为4.00%,CINⅠ级组PCNA阳性过表达率为32.14%,CINⅡ/Ⅲ级组PCNA阳性过表达率为91.43%。对照组与CINⅠ级组、对照组与CINⅡ/Ⅲ级组PCNA阳性表达率比较,差异均有统计学意义(χ^(2)=18.15、23.60,均P<0.05);CINⅠ级组与CINⅡ/Ⅲ级组PCNA阳性表达率比较,差异无统计学意义(χ^(2)=0.01,P>0.05);但CINⅡ/Ⅲ级组与CINⅠ级组PCNA阳性过表达率比较,差异有统计学意义(χ^(2)=22.97,P<0.05)。MVD在对照组、CINⅠ级组及CINⅡ/Ⅲ级组中的表达水平分别为(12.92±4.01)、(21.36±6.14)及(29.79±5.68);CINⅠ级组与CINⅡ/Ⅲ级组MVD表达均明显高于对照组,差异均有统计学意义(t=5.883、12.727,均P<0.05);CINⅡ/Ⅲ级组MVD表达明显高于CINⅠ级组,差异有统计学意义(t=5.645,P<0.05);MVD表达随宫颈病变级别升高而呈增加趋势。Pearson相关性分析显示,PCNA阳性表达与MVD值呈正相关关系(r=0.595,P<0.05)。受试者工作特征(ROC)曲线显示,应用PCNA和MVD联合诊断CINⅡ/Ⅲ级的价值明显高于二者单独诊断,PCNA与MVD诊断CINⅡ/Ⅲ级的最佳截点分别为≥2.94和≥21.50。结论宫颈组织中PCNA阳性表达与MVD计数随着宫颈病变程度的增加而增加,CIN患者宫颈组织中的PCNA和MVD呈正相关关系,且二者联合检测对于CINⅡ/Ⅲ级具有较高的诊断价值,可发现高度病变倾向的存在,提高宫颈病变的诊断率,并指导临床治疗,避免治疗不足和过度治疗。

Objective To study the expression characteristics of proliferating cell antigen(PCNA) and microvessel density(MVD) in cervical tissues,and to explore the diagnostic value of their combined application.Methods Patients who underwent cervical liquid-based thin-layer cytology and high-risk human papillomavirus(HPV) detection in Hangzhou Third People's Hospital from December 2018 to December 2020 were selected as the research objects.According to the diagnostic criteria of cervical/vaginal cytology by the International Cancer Association,patients with abnormal or normal cervical liquid-based thin-layer cytology screening and positive HPV16 or 18 were performed colposcopy cervical biopsy.Sixty-three patients with cervical intraepithelial neoplasia(CIN) confirmed by pathological diagnosis who underwent loop electrosurgical excision procedure or cold knife conization were the observation group,including 28 patients with CINⅠ grade and 35 patients with CINⅡ/Ⅲ grade.In addition,25 patients who underwent hysterectomy for hysteromyoma and were diagnosed as normal cervical tissue by pathology were selected as the control group.Paraffin specimens of all patients were observed,and PCNA and MVD immunohistochemical staining were performed in the most serious lesion area.Results The positive expression rate of PCNA in the control group was 64.00%.The positive expression rate of PCNA in CINⅠ grade group was 96.43%.The positive expression rate of PCNA in CINⅡ/Ⅲ grade group was 100.00% respectively.The positive overexpression rate of PCNA was 4.00% in control group,32.14% in CINⅠ grade group and 91.43% in CINⅡ/Ⅲ grade group.The positive expression rate of PCNA in the control group was significantly different from that in the CINⅠ group and between the control group and the CINⅡ/Ⅲ group(χ~2=18.15,23.60,all P<0.05).There was no significant difference in the positive expression rate of PCNA between CINⅠgrade group and CINⅡ/Ⅲ grade group(χ~2=0.01,P<0.05).However,there was a significant difference in the positive overexpression rate of PCNA between CINⅡ/Ⅲ grade group and CINⅠ grade group(χ~2=22.97,P<0.05).The expression levels of MVD in control group,CINI grade group and CINⅡ/Ⅲ grade group were(12.92±4.01),(21.36±6.14) and(29.79±5.68) respectively.The expression of MVD in CINⅠ grade group and CINⅡ/Ⅲ grade group was significantly higher than that in the control group(t=5.883,12.727,all P<0.05),and that in CINⅡ/Ⅲ grade group was significantly higher than that in CINⅠ grade group(t=5.645,P<0.05).The expression of MVD increased with the increase of cervical lesions.Pearson correlation analysis showed that the positive expression of PCNA was positively correlated with MVD(r=0.595,P<0.05).The curve of receiver's operating characteristics(ROC) showed that the value of combined diagnosis of PCNA and MVD for CINⅡ/Ⅲ grade was significantly higher than that of both alone.The best cut-off points of PCNA and MVD in the diagnosis of CINⅡ/Ⅲ grade were ≥2.94 and ≥21.50,respectively.Conclusion PCNA positive expression and MVD count in cervical tissue increase with the increase of cervical lesions.There was a positive correlation between PCNA and MVD in cervical tissue of CIN patients,and the combined detection of PCNA and MVD has high diagnostic value for CINⅡ/Ⅲ grade,which can find the existence of high pathological tendency,improve the diagnostic rate of cervical lesions,guide treatment,and avoid insufficient and excessive treatment.