文章摘要

NRF2联合p16和Ki-67在宫颈鳞状上皮内病变中的表达及诊断价值

作者: 1刘丹阳, 2朱兴华, 2卫颖泽
1 复旦大学附属妇产科医院病理科，上海 200090
2 南通大学附属肿瘤医院/南通市肿瘤医院病理科，江苏 南通 226361
通讯: 卫颖泽 Email: ntwzeze@163.com
DOI: 10.3978/j.issn.2095-6959.2022.08.010
基金: 国家自然科学基金(82103062)；南通市卫健委面上课题(MA2021019，MB2020019)。

摘要

目的：探讨核转录因子E2相关因子2(NF-E2-related factor 2，NRF2)联合p16、Ki-67在宫颈鳞状上皮内病变(squamous intraepithelial lesions，SIL)诊断中的价值。方法：采用免疫组织化学方法检测49例良性/反应性宫颈鳞状上皮、102例低级别鳞状上皮内病变(low-grade squamous intraepithelial lesion，LSIL)、101例高级别鳞状上皮内病变(high-grade squamous intraepithelial lesion，HSIL)中NRF2、p16和Ki-67的表达情况，并评估单独使用或联合使用这些指标在宫颈SIL中的诊断效能。结果：1)NRF2、p16和Ki-67在良性/反应性组、LSIL组、HSIL组的阳性表达率均呈逐渐上升趋势，各指标在3组之间的表达差异均有统计学意义(均P<0.05)；2)受试者工作特征(receiver operator characteristic，ROC)曲线检验良性/反应性宫颈和LSIL的结果显示NRF2、p16和Ki-67的曲线下面积分别为0.631、0.921、0.735(均P<0.05)，二者联合或三者联合后曲线下面积均较单独指标组高(均P<0.05)；3)ROC曲线检验良性/反应性宫颈和HSIL的结果显示NRF2、p16和Ki-67的曲线下面积分别为0.897、0.997、0.906(均P<0.05)，二者联合或三者联合后曲线下面积均较单独指标组高(均P<0.05)；4)ROC曲线检验LSIL和HSIL的结果显示NRF2、p16和Ki-67的曲线下面积分别为0.864、0.916、0.793(均P<0.05)，二者联合或三者联合后曲线下面积均较单独指标组高(均P<0.05)。结论：NRF2在HSIL中的阳性表达率显著高于LSIL，随着宫颈病变级别提高，NRF2表达强度也逐渐增强。NRF2联合p16和Ki-67能够提高宫颈SIL病理诊断的准确性。
关键词： 核转录因子E2相关因子2；p16；Ki-67；鳞状上皮内病变

Expression and diagnostic value of NRF2 combined with p16 and Ki-67 in cervical squamous intraepithelial lesions

Authors: 1LIU Danyang, 2ZHU Xinghua, 2WEI Yingze
1 Department of Pathology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai 200090, China
2 Department of Pathology, Affiliated Tumor Hospital of Nantong University/Nantong Tumor Hospital, Nantong Jiangsu 226361, China

CorrespondingAuthor: WEI Yingze Email: ntwzeze@163.com

DOI: 10.3978/j.issn.2095-6959.2022.08.010

Foundation: This work was supported by the National Natural Science Foundation (82103062), and General Project of Nantong Health Commission (MA2021019, MB2020019), China.

Abstract

Objective: To explore the value of NF-E2-related factor 2 (NRF2) combined with p16 and Ki-67 in the diagnosis of cervical squamous intraepithelial lesions (SIL). Methods: The expressions of NRF2, p16 and Ki-67 in 49 cases of benign/reactive cervical squamous epithelium, 102 cases of low-grade squamous intraepithelial lesion (LSIL), and 101 cases of high-grade squamous intraepithelial lesion (HSIL) were detected by immunohistochemistry, and the diagnostic efficacy of these makers alone or in combination in cervical SIL was evaluated. Results: 1) The positive expression rates of NRF2, p16 and Ki-67 increased gradually in benign/reactive, LSIL, and HSIL group, and the difference in the expression of each marker among the 3 groups was statistically significant (P<0.05). 2) ROC curve test of benign/reactive cervix and LSIL showed that the area under the curve of NRF2, p16 and Ki-67 were 0.631, 0.921 and 0.735 (P<0.05), respectively. Each area under the curve in each group of the combination with 2 or 3 markers was higher than that in the group of single marker (P<0.05). 3) ROC curve test of benign/reactive cervix and HSIL showed that the area under the curve of NRF2, p16 and Ki-67 were 0.897, 0.997 and 0.906 respectively (P<0.05). Each area under the curve in each group of the combination with 2 or 3 markers was higher than that in the group of single marker (P<0.05). 4) ROC curve test of LSIL and HSIL showed that the area under the curve of NRF2, p16 and Ki-67 were 0.864, 0.916 and 0.793 respectively (P<0.05). Each area under the curve in each group of the combination with 2 or 3 markers was higher than that in the group of single marker (P<0.05). Conclusion: The positive expression rate of NRF2 in the HSIL is significantly higher than that in the LSIL, and as the grade of cervical lesions increases, the expression degrees of NRF2 also gradually increased. The use of NRF2 alone or in combination with p16 and Ki-67 could effectively improve the accuracy of pathological diagnosis of cervical squamous intraepithelial lesions.

Keywords： NF-E2-related factor 2; p16; Ki-67; squamous intraepithelial lesions

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