County Institute of Pulmonology, Torokbalint, Hungary.
Károly Rácz Doctoral School of Clinical Medicine, Semmelweis University, Budapest, Hungary.
Pathol Oncol Res. 2023 May 18;29:1611164. doi: 10.3389/pore.2023.1611164. eCollection 2023.
Our knowledge is still limited about the characteristics and treatment of rare lung tumors. The aim of our study was to determine programmed cell death ligand-1 (PD-L1) and programmed cell death-1 (PD-1) expression in rare pulmonary tumors to assess the potential role of immunotherapy. 66 pathologically confirmed rare lung tumors including 26 mucoepidermoid carcinomas (MECs), 27 adenoid cystic carcinomas (ACCs), and 13 tracheobronchial papillomas (TBPs) were collected retrospectively. Immunohistochemical (IHC) staining was performed on formalin fixed paraffin embedded (FFPE) tumor tissues, and PD-L1 expression on tumor cells (TCs) and immune cells (ICs), and PD-1 expression on ICs were determined. The cut off value for positive immunostaining was set at 1% for all markers. PD-L1 expression on TCs was observed in two cases of MEC (7.7%), one case of ACC (3.7%), and was absent in TBP samples. PD-L1 expression on ICs could be demonstrated in nine cases of MEC (34.6%), four cases of ACC (14.8%), and was absent in TBPs. All PD-L1 TC positive tumors were also PD-L1 IC positive. Higher expression level than 5% of PD-L1 TC and/or IC was observed only in one ACC and in two MEC patients. Among them, strong PD-L1 immunopositivity of >50% on TCs and of >10% on ICs could be demonstrated in one MEC sample. PD-L1 expression of ≥1% on ICs was significantly more common in MEC, than in TBP ( < 0.001). In MEC ≥1% PD-L1 TC or IC expressions were significantly more common in patients aged 55 or older, than in younger patients ( = 0.046, and = 0.01, respectively). PD-1 expression on ICs was found in five cases of MEC (19.2%), four cases of ACC (14.8%), and in two cases of TBP (15.4%). Only one MEC case showed a higher than 5% expression level of PD-1 on ICs. This retrospective study comprehensively demonstrated the rare expression of PD-L1 and PD-1 in pulmonary MEC, ACC, and TBP. However, we found very strong PD-L1 immunopositivity on both TCs and ICs in one MEC sample, which warrants further investigations in a larger cohort.
我们对罕见肺部肿瘤的特征和治疗方法的了解仍然有限。我们的研究目的是确定程序性细胞死亡配体 1(PD-L1)和程序性细胞死亡 1(PD-1)在罕见肺肿瘤中的表达,以评估免疫治疗的潜在作用。
本研究回顾性收集了 66 例经病理证实的罕见肺部肿瘤,包括 26 例黏液表皮样癌(MEC)、27 例腺样囊性癌(ACC)和 13 例气管支气管乳头状瘤(TBP)。对福尔马林固定石蜡包埋(FFPE)肿瘤组织进行免疫组织化学(IHC)染色,确定肿瘤细胞(TCs)和免疫细胞(ICs)上的 PD-L1 表达以及 ICs 上的 PD-1 表达。所有标志物的阳性免疫染色截断值均设为 1%。
在 2 例 MEC(7.7%)、1 例 ACC(3.7%)中观察到 PD-L1 在 TCs 上的表达,而在 TBP 样本中未见表达。在 9 例 MEC(34.6%)、4 例 ACC(14.8%)中可检测到 PD-L1 在 ICs 上的表达,而 TBP 中未见表达。所有 PD-L1 TC 阳性肿瘤均为 PD-L1 IC 阳性。仅在 1 例 ACC 和 2 例 MEC 患者中观察到 TC 和/或 IC 上 PD-L1 表达水平高于 5%。其中,1 例 MEC 样本中 TCs 上的强 PD-L1 免疫阳性率>50%,ICs 上的 PD-L1 免疫阳性率>10%。在 MEC 中,IC 上 PD-L1 表达≥1%的情况明显多于 TBP(<0.001)。在 MEC 中,年龄≥55 岁的患者与年龄较小的患者相比,TC 或 IC 上 PD-L1 TC 或 IC 表达≥1%的情况更为常见(=0.046 和=0.01)。在 5 例 MEC(19.2%)、4 例 ACC(14.8%)和 2 例 TBP(15.4%)中发现了 PD-1 在 ICs 上的表达。只有 1 例 MEC 病例在 ICs 上显示 PD-1 表达水平高于 5%。
这项回顾性研究全面显示了肺部 MEC、ACC 和 TBP 中 PD-L1 和 PD-1 的罕见表达。然而,我们在 1 例 MEC 样本中发现了 TC 和 IC 上非常强的 PD-L1 免疫阳性,这需要在更大的队列中进一步研究。