Salih Shahenaz S, Abdelaziz Mohammed S, Abdelhag Ibtehal M, Mosad Altaf S
Department of Histopathology and Cytology, Sudan University of Science and Technology, Khartoum, Sudan.
Department of Histopathology & Cytology, Omdurman Islamic University, Khartoum, Sudan.
J Taibah Univ Med Sci. 2023 Sep 7;19(1):99-105. doi: 10.1016/j.jtumed.2023.08.006. eCollection 2024 Feb.
This study aimed to investigate the protein expression of programmed death ligand 1 (PD-L1) in breast cancer (BC) tissues and link this data with estrogen status, the expression of interferon regulatory factor1 (IRF-1), and CD8+T lymphocyte infiltration by immunohistochemistry (IHC). We also attempted to identify the association between PD-L1 expression, the cell proliferation index marker (Ki67), and lymph node involvement.
One hundred and fifty formalin-fixed and paraffin-embedded (FFPE) blocks of breast tissue were acquired from Sudanese females The National Public Health Laboratory. FFPE blocks were subjected to antigen/antibody detection by IHC with antibodies raised against PD-L1, IRF1, and CD8. These data were analyzed alongside data extracted from medical records relating to estrogen receptor (ER) status, Ki67 index, and lymph node (LN) status.
IHC analysis revealed a significant association between PD-L1 and CD8 (p = 0.010). In addition, regression analysis indicated the ability of IRF1 to induce PD-L1 expression levels in IRF1-positive cases that were two-fold higher than IRF1-deficient cases (odds ratio [OR]: 2.441 p = 0.035). Analysis also suggested that PD-L1 exerts impact on cell proliferation, as reflected by the Ki67 index. An independent t test showed that higher Ki67 scores were more frequent among PD-L1-positive patients than in PD-L1-negative patients (t = 2.608 p = 0.014). There was an inverse association between PD-L1 and ER status; ER-positive tumors exhibited negative PD-L1 expression and (p = 0.04). Furthermore, we investigated the prognostic value of PD-L1 by evaluating the association between PD-L1 and LNs dispersed variably with tumor cells; there was no statistically significant relationship between these factors (p > 0.05).
The expression of PD-L1 and IRF-1, along with the infiltration of CD8, represents a potent panel of biomarkers with which to identify BC patients with the highest probabilities of achieving an excellent response to immune therapy, particularly when taking ER status into account, as ER expression levels are known to be high when immune checkpoint blockers (ICBs) generate a poor response.
本研究旨在通过免疫组织化学（IHC）研究程序性死亡配体1（PD-L1）在乳腺癌（BC）组织中的蛋白表达，并将该数据与雌激素状态、干扰素调节因子1（IRF-1）的表达以及CD8 + T淋巴细胞浸润相关联。我们还试图确定PD-L1表达、细胞增殖指数标志物（Ki67）与淋巴结受累之间的关联。
从苏丹女性国家公共卫生实验室获取150个福尔马林固定石蜡包埋（FFPE）的乳腺组织块。用针对PD-L1、IRF1和CD8的抗体通过IHC对FFPE组织块进行抗原/抗体检测。这些数据与从有关雌激素受体（ER）状态、Ki67指数和淋巴结（LN）状态的医疗记录中提取的数据一起进行分析。
IHC分析显示PD-L1与CD8之间存在显著关联（p = 0.010）。此外，回归分析表明IRF1在IRF1阳性病例中诱导PD-L1表达水平的能力是IRF1缺陷病例的两倍（优势比[OR]：2.441，p = 0.035）。分析还表明，PD-L1对细胞增殖有影响，如Ki67指数所示。独立t检验显示，PD-L1阳性患者的Ki67评分高于PD-L1阴性患者（t = 2.608，p = 0.014）。PD-L1与ER状态呈负相关；ER阳性肿瘤表现出PD-L1阴性表达（p = 0.04）。此外，我们通过评估PD-L1与肿瘤细胞分散的淋巴结之间的关联来研究PD-L1的预后价值；这些因素之间没有统计学上的显著关系（p>0.05）。
PD-L1和IRF-1的表达以及CD8的浸润代表了一组有效的生物标志物，可用于识别对免疫治疗有最佳反应可能性最高的BC患者，特别是在考虑ER状态时，因为已知当免疫检查点阻断剂（ICB）产生较差反应时ER表达水平较高。
