Hospital Garcia de Orta, Almada, Portugal.
Pathology, Champalimaud Clinical Centre, Champalimaud Foundation, Avenida Brasília, 1400-038, Lisbon, Portugal.
Virchows Arch. 2024 Mar;484(3):507-516. doi: 10.1007/s00428-023-03580-z. Epub 2023 Jun 21.
Programmed death-ligand 1 (PD-L1) is overexpressed in cervical carcinoma, hindering tumor destruction. The aim of this study was to assess PD-L1 expression by immunohistochemistry in cervical squamous cell carcinoma (SCC) and squamous intraepithelial lesions (SILs) from human immunodeficiency virus-positive (HIV+) and human immunodeficiency virus-negative (HIV-) patients. A total of 166 SCC and SIL samples of HIV+ and HIV- patients were included and analyzed for PD-L1 expression through tumor proportion score (TPS), and results were stratified in five TPS groups using SP263 antibody and, combined positive score (CPS) using 22C3 antibody. In cohort 1 (SP263 clone), all HIV+ patients were negative for intraepithelial lesion or malignancy (NILM), and low-grade squamous intraepithelial lesions (LSILs) scored < 1; and 87.5% of high-grade squamous intraepithelial lesions (HSILs) adjacent to SCC, 19% of HSILs non-adjacent to SCC, and 69% of SCCs scored ≥ 1 (15.4% scored 5). In HIV- patients, all NILM, LSILs, HSILs adjacent to SCC, and two HSILs non-adjacent to SCC scored < 1. SCC: 88.2% scored ≥ 1 and 5.9% scored 5. In cohort 2 (SP263 and 22C3 clones), 16.7% of HIV+ patients with SCC were positive with both clones, CPS ≥ 1 (22C3) or score 5 (≥ 50%) (SP263), showing no significant differences in positivity between both clones. These results indicate that a relatively low percentage of SCCs (16.7%; both in HIV+ and in HIV- patients) express PD-L1 (TPS ≥ 50% and CPS > 1), which may be due to some samples being archival material, sample characteristics, or use of different methodologies, highlighting the need for standardization of PD-L1 assessment in SCC of the cervix. The fact that PD-L1 is overexpressed in SILs of HIV+ patients suggests potential additional applications for immunotherapy in this disease.
程序性死亡配体 1（PD-L1）在宫颈癌中过度表达，阻碍肿瘤破坏。本研究旨在通过免疫组织化学评估人免疫缺陷病毒阳性（HIV+）和人免疫缺陷病毒阴性（HIV-）患者的宫颈鳞状细胞癌（SCC）和鳞状上皮内病变（SIL）中 PD-L1 的表达。共纳入 166 例 HIV+和 HIV-患者的 SCC 和 SIL 样本，通过肿瘤比例评分（TPS）分析 PD-L1 表达，并使用 SP263 抗体和 22C3 抗体进行组合阳性评分（CPS），将结果分为 5 个 TPS 组。在队列 1（SP263 克隆）中，所有 HIV+患者的上皮内病变或恶性程度均为阴性（NILM），低级别鳞状上皮内病变（LSILs）评分<1；高级别鳞状上皮内病变（HSILs）与 SCC 相邻的占 87.5%，与 SCC 不相邻的 HSILs 占 19%，SCC 评分≥1 的占 69%（15.4%评分 5）。在 HIV-患者中，所有 NILM、LSILs、HSILs 与 SCC 相邻，以及两个 HSILs 与 SCC 不相邻，评分均<1。SCC：88.2%评分≥1，5.9%评分 5。在队列 2（SP263 和 22C3 克隆）中，16.7%的 HIV+SCC 患者两种克隆均为阳性，CPS≥1（22C3）或评分 5（≥50%）（SP263），两种克隆的阳性率无显著差异。这些结果表明，相对较低比例的 SCC（16.7%；HIV+和 HIV-患者均有）表达 PD-L1（TPS≥50%和 CPS>1），这可能是由于部分样本为存档材料、样本特征或使用不同的方法学，突出了在宫颈癌 SCC 中 PD-L1 评估标准化的必要性。PD-L1 在 HIV+患者的 SILs 中过度表达表明免疫治疗在该疾病中有潜在的额外应用。
