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中华乳腺病杂志(电子版)

中华乳腺病杂志(电子版) ›› 2018, Vol. 12 ›› Issue (05) : 294 -298. doi: 10.3877/cma.j.issn.1674-0807.2018.05.007

所属专题： 文献；

论著

三阴性乳腺癌中程序性死亡配体1的表达及其与PTEN基因的关系
魏开鹏1, 陈海莺2, 陈燕红1, 邱建龙1,†()   
  1. 1. 362000　泉州，解放军第180医院病理科
    2. 362000　泉州，解放军第180医院外科
  • 收稿日期:2017-12-07 出版日期:2018-10-01
  • 通信作者: 邱建龙

Expression of programmed death ligand 1 in triple negative breast cancer and its relationship with PTEN

Kaipeng Wei1, Haiying Chen2, Yanhong Chen1, Jianlong Qiu1,†()   

  1. 1. Department of Pathology, No.180 Hospital of PLA, Quanzhou 362000, China
    2. Department of Surgery, No.180 Hospital of PLA, Quanzhou 362000, China
  • Received:2017-12-07 Published:2018-10-01
  • Corresponding author: Jianlong Qiu
  • About author:
    Corresponding author: Qiu Jianlong, Email:
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魏开鹏, 陈海莺, 陈燕红, 邱建龙. 三阴性乳腺癌中程序性死亡配体1的表达及其与PTEN基因的关系[J]. 中华乳腺病杂志(电子版), 2018, 12(05): 294-298.

Kaipeng Wei, Haiying Chen, Yanhong Chen, Jianlong Qiu. Expression of programmed death ligand 1 in triple negative breast cancer and its relationship with PTEN[J]. Chinese Journal of Breast Disease(Electronic Edition), 2018, 12(05): 294-298.

目的

探讨程序性死亡配体1(PD-L1)在三阴性乳腺癌(TNBC)中的表达情况及其与PTEN基因的关系。

方法

通过癌症基因组图谱(TCGA)数据库查询PD-L1 mRNA在浸润性乳腺癌数据集(包括115例TNBC和702例非TNBC)中的表达情况。收集2012年1月至2016年12月解放军第180医院收治的182例浸润性乳腺癌术后石蜡包埋组织标本，包括62例TNBC和120例非TNBC，并用免疫组织化学方法检测PD-L1和PTEN的表达情况。用t检验比较TCGA数据库中2组的PD-L1 mRNA表达量，率的比较用χ2检验，Mann-Whitney U秩和检验比较石蜡标本中2组PD-L1表达强度，并用χ2检验和Spearman秩相关检验分析PD-L1与PTEN表达的相关性。

结果

TCGA数据库分析显示，浸润性乳腺癌中3.8%(31/817)有PD-L1 mRNA上调，其中TNBC组的表达上调率为8.7%(10/115)，高于非TNBC组的3.0%(21/702)(χ2＝7.314，P＝0.007)，TNBC组的PD-L1 mRNA表达量为8.05±0.91，高于非TNBC组的7.38±0.73 (t＝7.510，P<0.001)。石蜡标本的免疫组织化学结果显示，TNBC组的PD-L1阳性表达率为14.5%(9/62)，高于非TNBC组的5.0% (6/120)(χ2＝4.895，P＝0.027)，而且PD-L1阳性表达强度也高于非TNBC组(Z＝－2.291，P＝0.022)。TNBC石蜡标本中PD-L1与PTEN蛋白表达呈负相关(χ2＝6.913，P＝0.009; r＝－0.382，P＝0.002)。

结论

TNBC中PD-L1表达高于非TNBC，并与PTEN负相关，其可能成为TNBC患者的免疫治疗靶点。

关键词: 乳腺肿瘤, 免疫组织化学, PTEN磷酸水解酶
Objective

To investigate the expression of programmed death ligand 1(PD-L1) in triple negative breast cancer (TNBC) and its relationship with PTEN expression.

Methods

In the Cancer Genome Atlas (TCGA) database, the expression of PD-L1 mRNA in the invasive breast cancer dataset was analyzed, including 115 TNBC cases and 702 non-TNBC cases. A total of 182 paraffin-embedded tissue specimens from invasive breast cancer patients admitted to the No.180 Hospital of PLA from January 2012 to December 2016 were collected and the expression of PD-L1 and PTEN was immunohistochemically detected. PD-L1 mRNA expression was compared between two groups in TCGA database using t test. χ2 test was used to compare the rates. The intensity of PD-L1 positive expression in paraffin-embedded specimens were compared between two groups using Mann-Whitney U test. χ2 test and Spearman rank test were used to analyze the correlation between PD-L1 and PTEN expression.

Results

In TCGA database, PD-L1 mRNA level was up-regulated in 3.8% (31/817) of invasive breast cancer. The up-regulation rate of PD-L1 mRNA in TNBC (8.7%, 10/115) was significantly higher than that in non-TNBC (3.0%, 21/702) (χ2=7.314, P=0.007). PD-L1 mRNA expression in TNBC was significantly higher than that in non-TNBC(8.05±0.91 vs 7.38±0.73, t=7.510, P<0.001). The immunohistological results of 182 paraffin-embedded tissue specimens showed that the positive expression rate of PD-L1 in TNBC (14.5%, 9/62) was significantly higher than that in non-TNBC(5.0%, 6/120)(χ2=4.895, P=0.027), and the expression intensity of PD-L1 in TNBC was significantly higher than that in non-TNBC(Z=-2.291, P=0.022). The PD-L1 protein expression was negatively correlated with PTEN protein expression in paraffin-embedded TNBC specimens (χ2=6.913, P=0.009, r=-0.382, P=0.002).

Conclusion

PD-L1, which shows higher expression in TNBC patients than in non-TNBC patients and a negative correlation with PTEN, may be a potential target for TNBC immunotherapy.

Key words: Breast neoplasms, Immunohistochemistry, PTEN phosphohydrolase
图1 浸润性乳腺癌标本中PD-L1和PTEN的蛋白表达　a图为TNBC组织病理图(HE ×200)；b图为TNBC组织PD-L1的免疫组织化学染色(×200)；c图为非TNBC组织PD-L1的免疫组织化学染色(×200)；d图为PD-L1免疫组织化学染色阴性对照图(×200)；e、f图为PD-L1阳性的TNBC标本，其中e图为PD-L1的免疫组织化学染色(×200)，阳性颗粒定位于细胞膜，f图为PTEN的免疫组织化学染色(×200)，未着色呈阴性；g、h图为PD-L1阴性的TNBC标本，其中g图为PD-L1的免疫组织化学染色(×200)，未着色呈阴性，h图为PTEN的免疫组织化学染色(×200)，阳性颗粒定位于细胞质
表1 182例浸润性乳腺癌中PD-L1蛋白的表达强度
组别 例数 PD-L1表达[例(%)]
－ ＋ ＋＋ ＋＋＋
TNBC 62 53(85.5) 1(1.6) 2(3.2) 6(9.7)
非TNBC 120 114(95.0) 2(1.7) 3(2.5) 1(0.8)
Z值 ? －2.291
P值 ? 0.022
表2 62例三阴性乳腺癌标本中PD-L1与PTEN蛋白表达的关系(例)
PD-L1 PTEN 合计
阳性 阴性
阳性 2 7 9
阴性 39 14 53
合计 41 21 62
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