Background and aim: About a third of Pituitary Neuroendocrine Tumors (PitNETs) may show aggressive behavior. Many efforts have been performed for identifying possible predictive factors to early determine the future behavior of PitNETs. Programmed cell death ligand 1 (PD-L1) expression was associated with a more aggressive biology in different solid tumors, but its role in PitNET is not well-established yet. Our study aims to analyze PD-L1 expression in a surgical cohort of PitNETs to determine its association with radiological invasion and pathology findings, as well as with long-term recurrence rates. Methods: We performed a retrospective analysis in a series of 86 PitNETs. Clinical presentation and radiological features of the preoperative period were collected, as well as pathological data and follow-up data. The rate of PD-L1 expression was immunohistochemically evaluated and expressed as a tumor proportion score (TPS). We assessed its relationship with cavernous sinus invasion and Trouillas’ classification as primary outcomes. Secondary outcomes included the TPS’ relationship with histopathological markers of proliferation, hormonal expression, tumor size and long-term recurrence rates. We calculated the optimal cut-point for the primary outcomes while maximizing the product of the sensitivity and specificity and then we evaluated the significance of secondary outcomes with logistic regression analysis. Results: Eighty-six patients were included in the analysis; 50 cases were non-functional PitNETs. The TPS for PD-L1 showed a highly right-skewed distribution in our sample, as 30.2% of patients scored 0. Using Trouillas’ classification, we found that “proliferative” cases have a significantly higher probability to express PD-L1 in more than 30% of tumor cells (OR: 5.78; CI 95%: 1.80–18.4). This same cut-point was also associated with p53 expression. A positive association was found between PD-L1 expression and GH expression (p= 0.001; OR: 5.44; CI 95%: 1.98–14.98), while an inverse relationship was found with FSH/LH expression (p= 0.014; OR = 0.27, CI 95%: 0.10–0.76). No association was found with CS invasion, tumor size, bone erosion or dura invasion. We could not find any association between PD-L1 expression and recurrence. Conclusions: PD-L1 expression was associated with proliferative grades of Trouillas’ classification and p53 expression. We also confirmed a higher expression of PD-L1 in somatotroph tumors. Larger studies are necessary to investigate the relationship between PD-L1 expression and aggressive behaviors.
背景与目的：约三分之一的垂体神经内分泌肿瘤（PitNETs）可能表现出侵袭性行为。为早期预测PitNETs的生物学行为，学界已开展大量研究以探寻潜在预测因子。程序性死亡配体1（PD-L1）的表达与多种实体肿瘤的侵袭性生物学行为相关，但其在PitNETs中的作用尚未明确。本研究旨在通过分析手术切除PitNETs样本中PD-L1的表达情况，探究其与影像学侵袭特征、病理学表现及远期复发率之间的关联。方法：我们对86例PitNETs病例进行回顾性分析，收集患者术前临床表现、影像学特征、病理学资料及随访数据。采用免疫组织化学法检测PD-L1表达水平，以肿瘤比例评分（TPS）进行量化。主要研究终点为PD-L1表达与海绵窦侵犯及Trouillas分级系统的关联性，次要研究终点包括TPS与增殖组织病理学标志物、激素表达类型、肿瘤体积及远期复发率的关系。通过最大化敏感度与特异度乘积确定主要研究终点的最佳截断值，并采用逻辑回归分析评估次要研究终点的统计学意义。结果：本研究共纳入86例患者，其中50例为非功能性PitNETs。PD-L1的TPS评分呈高度右偏分布，30.2%的患者评分为0。根据Trouillas分级系统，我们发现"增殖型"病例在超过30%肿瘤细胞中表达PD-L1的概率显著增高（比值比：5.78；95%置信区间：1.80–18.4）。该截断值同样与p53表达相关。PD-L1表达与生长激素表达呈正相关（p=0.001；比值比：5.44；95%置信区间：1.98–14.98），而与卵泡刺激素/黄体生成素表达呈负相关（p=0.014；比值比=0.27，95%置信区间：0.10–0.76）。未发现PD-L1表达与海绵窦侵犯、肿瘤体积、骨质侵蚀或硬脑膜侵犯存在关联，亦未发现其与肿瘤复发存在统计学关联。结论：PD-L1表达与Trouillas分级系统中的增殖分级及p53表达相关，同时在生长激素型肿瘤中呈现更高表达水平。PD-L1表达与侵袭性行为的关系仍需更大规模研究进一步验证。
PD-L1 Expression in Pituitary Neuroendocrine Tumors/Pituitary Adenomas
肿瘤(癌症)患者之家