程序性死亡受体1配体、拓扑异构酶Ⅱα及p16蛋白在子宫颈癌中的表达及其意义

Expression of programmed death-ligand 1, topoisomerase Ⅱα and p16 proteins in cervical cancer and their significances

目的分析程序性死亡受体1配体（PD-L1）、p16蛋白及DNA拓扑异构酶Ⅱα（TOPOⅡα）在子宫颈癌中的表达及其临床意义。方法选取2014年1月至2015年12月手术切除或活组织检查的子宫颈石蜡样本199例，包括子宫颈鳞状细胞浸润癌106例，高级别与低级别子宫颈上皮内瘤变（CIN）各30例，子宫颈正常组织33例。采用EnVision方法进行PD-L1、p16、TOPOⅡα免疫组织化学检测。结果PD-L1阳性表达率在子宫颈鳞状细胞浸润癌中为66.0%（70/106），但在高级别、低级别CIN和正常子宫颈组织中均不表达，差异均有统计学意义（均P=0.000）；在鳞状细胞浸润癌中，低分化组阳性率[77.3%（51/66）]高于中高分化组[56.5%（21/40）]，差异有统计学意义（χ2=7.02，P=0.01）。依据国际妇产科协会（FIGO）分期，Ⅰ~Ⅱ期阳性率[54.9%（28/51）]低于Ⅲ~Ⅳ期[76.4%（42/55）]，差异有统计学意义（χ2=5.47，P=0.02）。PD-L1表达与病灶大小和淋巴结转移均无关（均P〉0.05）。p16阳性表达率在子宫颈鳞状细胞浸润癌中为99.1%（105/106），在高级别CIN中为86.7%（26/30），低级别中为26.7%（8/30），在正常子宫颈组织中不表达，差异均有统计学意义（均P〈0.01）。p16的表达与组织学分化程度、FIGO分期、病灶大小、淋巴结转移均无关（均P〉0.05）。TOPOⅡα阳性表达率在子宫颈鳞状细胞浸润癌中为97.2%（103/106），与高级别CIN[73.3%（22/30）]、低级别CIN[66.7%（20/30）]及在正常子宫颈组织（不表达）比较，差异均有统计学意义（均P=0.000）。TOPOⅡα阳性表达率在高级别CIN与低级别间差异无统计学意义（χ2=0.32，P=0.570）。TOPOⅡα的表达与组织学分化程度、FIGO分期、病灶大小、淋巴结转移均无关（均P〉0.05）。结论PD-L1、p16、TOPOⅡα表达与子宫颈癌的侵袭有关。PD-L1可能成为子宫颈浸润性癌患者免疫治疗的免疫检测点。

ObjectiveTo analyze the expression of programmed death ligand 1 （PD-L1）, p16 proteins and DNA topoisomerase Ⅱα （TOPOⅡα） in cervical cancer and their clinical significances.MethodsA total of 181 paraffin-embedded operating specimens and the biopsy including 106 cervical squamous cell carcinoma, 30 high grade cervical intraepithelial neoplasia （CIN）, 30 low grade CIN and 33 normal cervical were selected from January 2014 to December 2015. An immunohistochemical EnVision method was used to detect the expression of PD-L1, p16 and TOPOⅡα. ResultsThe positive rate of PD-L1 expression in cervical squamous cell carcinoma was 66.0% （70/106）, but it was not expressed in high grade CIN, low grade CIN and normal cervical tissues, the differences were statistically significant （all P= 0.000）. Whereas, in squamous cell carcinoma, the positive rate of PD-L1 in poor differentiation group [77.3% （51/66）] was higher than that in middle or high differentiation group [56.5% （21/40）], and the difference was statistically significant （χ2= 7.02,P= 0.01）. According to the FIGO stage, the positive rate in stage Ⅰ-Ⅱ group [54.9% （28/51）] was lower than that in stage Ⅲ-Ⅳ group [76.4% （42/55）], and the difference was statistically significant （χ2= 5.47, P= 0.02）. But there was no statistical significance in lesion size or lymph node metastasis （both P 〉 0.05）. The positive rate of p16 in cervical squamous cell carcinoma was 99.1% （105/106）, in high grade CIN was 86.7% （26/30）, in low grade CIN was 26.7% （8/30）, and no expression in normal cervical tissues, the differences were statistically significant （all P 〈 0.001）. The expression of p16 had no relationship with histological differentiation, FIGO stage, lesion size, and lymph node metastasis （all P 〉 0.05）. The positive expression rate of TOPOⅡα in cervical squamous cell carcinoma was 97.2% （103/106）, compared with that in high grade CIN [73.3% （22/30）], low grade CIN [66.7% （20/30）], and normal cervical tissues （no expression）, the differences were statistically significant （all P= 0.000）. But there was no significant difference in the positive expression rate of TOPO Ⅱα between high grade and low grade CIN （χ2= 0.32, P= 0.570）. The expression of TOPOⅡα had no relationship with histological differentiation, FIGO stage, lesion size and lymph node metastasis （all P 〉 0.05）.ConclusionThe expression of PD-L1, p16 and TOPOⅡα is associated with the invasion of cervical cancer.PD-L1 may be an immune checkpoint for the treatment of patients with invasive cervical cancer.