Department of Neurology and Neurorehabilitation, BDH Hospital Hessisch Oldendorf, Hessisch Oldendorf, Germany.
Department for Rheumatology and Immunology, Hannover Medical School, Hannover, Germany.
Urol Int. 2022;106(11):1168-1176. doi: 10.1159/000525016. Epub 2022 Jun 2.
Programmed death-1 ligand (PD-L1) has been often studied in different types of renal-cell carcinoma (RCC). For example, in clear-cell renal carcinoma it is well established that programmed death-1 receptor and PD-L1 are important prognostic markers. In contrast, the role of programmed death-2 ligand (PD-L2) as prognostic marker remains unclear. The aim of this study was to evaluate if PD-L2 expression could play a role as a prognostic marker for papillary RCC (pRCC).
The patients' sample collection was a joint collaboration of the PANZAR consortium. Patients' medical history and tumor specimens were collected from n = 240 and n = 128 patients with type 1 and 2 pRCC, respectively. Expression of PD-L2 was determined by immunohistochemistry. In total, PD-L2 staining was evaluable in 185 of 240 type 1 and 99 of 128 type 2 pRCC cases.
PD-L2 staining was positive in 67 (36.2%) of type 1 and in 31 (31.3%) of type 2 pRCC specimens. The prevalence of PD-L2+ cells was significantly higher in high-grade type 1 tumors (p = 0.019) and in type 2 patients with metastasis (p = 0.002). Kaplan-Meier analysis disclosed significant differences in 5-year overall survival (OS) for patients with PD-L2- compared to PD-L2+ in pRCC type 1 of 88.4% compared to 73.6% (p = 0.039) and type 2 of 78.8% compared to 39.1% % (p < 0.001). However, multivariate analysis did not identify the presence of PD-L2+ cells neither in type 1 nor type 2 pRCC as an independent predictor of poor OS.
DISCUSSION/CONCLUSION: PD-L2 expression did not qualify as an independent prognostic marker in pRCC. Future studies will have to determine whether anti-PD-L2-targeted treatment may play a role in pRCC and expression can potentially serve as a predictive marker for these therapeutic approaches.
程序性死亡配体 1（PD-L1）在不同类型的肾细胞癌（RCC）中经常被研究。例如，在透明细胞肾细胞癌中，程序性死亡受体 1 和 PD-L1 是重要的预后标志物已得到充分证实。相比之下，程序性死亡配体 2（PD-L2）作为预后标志物的作用仍不清楚。本研究旨在评估 PD-L2 表达是否可作为乳头状 RCC（pRCC）的预后标志物。
患者样本采集是 PANZAR 联合研究的合作项目。从 n = 240 例 1 型和 n = 128 例 2 型 pRCC 患者中分别收集了患者的病史和肿瘤标本。通过免疫组织化学法测定 PD-L2 的表达。总共，185 例 1 型和 99 例 2 型 pRCC 病例可评估 PD-L2 染色。
PD-L2 染色在 67 例（36.2％）1 型和 31 例（31.3％）2 型 pRCC 标本中呈阳性。高分级 1 型肿瘤中 PD-L2+细胞的发生率明显更高（p = 0.019），转移的 2 型患者中 PD-L2+细胞的发生率更高（p = 0.002）。Kaplan-Meier 分析显示，1 型 pRCC 中 PD-L2-患者的 5 年总生存率（OS）与 PD-L2+患者相比为 88.4％比 73.6％（p = 0.039），2 型患者的 5 年总生存率（OS）为 78.8％比 39.1％（p < 0.001）。但是，多变量分析并未确定 1 型和 2 型 pRCC 中 PD-L2+细胞的存在是 OS 不良的独立预测因子。
讨论/结论：PD-L2 表达在 pRCC 中不能作为独立的预后标志物。未来的研究必须确定抗 PD-L2 靶向治疗是否在 pRCC 中发挥作用，并且表达可能作为这些治疗方法的预测标志物。
