Krzentowska Anna, Biesaga Beata, Czepko Ryszard, Merklinger-Gruchała Anna, Adamek Dariusz, Jasińska Małgorzata, Pluta Barbara, Michalska Wiktoria, Wróblewska Katarzyna, Janczy Filip, Gołkowski Filip
Department of Endocrinology and Internal Medicine, Medical College, Andrzej Frycz Modrzewski Krakow University, 30-705 Kraków, Poland.
Faculty of Health Sciences, Medical College, Andrzej Frycz Modrzewski Krakow University, 30-705 Kraków, Poland.
Int J Mol Sci. 2025 Aug 13;26(16):7830. doi: 10.3390/ijms26167830.
Pituitary neuroendocrine tumors (PitNETs), also known as pituitary adenomas, are rare tumors that are usually benign. At present, the WHO PitNET classification based on transcription factors is in force. A problem is caused by invasive tumors and silent tumors which, despite a lack of obvious clinical symptoms, tend to behave aggressively. Factors influencing the clinical course of these tumors are currently being sought. The aim of our study was to assess the expression of programmed death-ligand 1 (PD-L1) and proliferation biomarkers (Ki-67, cyclin D1, and P53) in PitNETs depending on the transcription factor and adenoma subtype. The analysis was performed in seventy-four patients operated on in a single neurosurgical center for pituitary tumors. Immunohistochemistry was performed for transcription factors and biomarkers-PD-L1, Ki-67, P53, and cyclin D1-in tissue microarray format. Membranous expression of PD-L1 was scored as 0 (no expression) and ≥1%. Nuclear expression of Ki-67 was scored at <3% and ≥3%, and the expression of P53 and cyclin D1 was scored at <10% and ≥10%. The following tumors expressed PD-L1 at ≥1%: gonadotroph, 21 (28.4%); corticotroph, 5 (6.7%); gonadotroph/lactotroph, 2 (2.7%); null cell adenoma, 3 (4.0%); multiple synchronous PitNET, 2 (2.7%); immature PIT-1 tumor, 1 (1.3%); mature PIT-1 tumor, 1 (1.5%). Ki-67 ≥ 3% was found in the following PitNETs: gonadotroph, 3 (4.0%); corticotroph, 2 (2.7%); lactotroph, 1 (1.3%); multiple synchronous PitNET, 1 (1.3%); immature PIT-1 tumor, 1 (1.3%); and mature PIT-1 tumor, 1 (1.3%). Patients with Ki-67 ≥ 3% were statistically significantly younger ( = 0.03). All tumors (100%) with a combination of cyclin D1 ≥ 10% and P53 < 10% were invasive on the Hardy scale. Of the four factors, PD-L1 increased the odds of invasiveness the most (adjusted OR = 2.35; 95% CI: 0.56-9.90). PD-L1 expression was present in some types of PitNETs. PD-L1 expression may help in identifying null cell adenomas. High cyclin D1 with low P53 may indicate greater tumor invasiveness.
垂体神经内分泌肿瘤（PitNETs），也称为垂体腺瘤，是一种通常为良性的罕见肿瘤。目前，基于转录因子的世界卫生组织垂体神经内分泌肿瘤分类正在实施。侵袭性肿瘤和无功能性肿瘤会引发问题，尽管缺乏明显的临床症状，但它们往往具有侵袭性。目前正在寻找影响这些肿瘤临床病程的因素。我们研究的目的是根据转录因子和腺瘤亚型评估垂体神经内分泌肿瘤中程序性死亡配体1（PD-L1）和增殖生物标志物（Ki-67、细胞周期蛋白D1和P53）的表达。该分析在一家单一神经外科中心接受垂体肿瘤手术的74例患者中进行。以组织芯片形式对转录因子和生物标志物——PD-L1、Ki-67、P53和细胞周期蛋白D1进行免疫组织化学检测。PD-L1的膜表达评分为0（无表达）和≥1%。Ki-67的核表达评分为<3%和≥3%，P53和细胞周期蛋白D1的表达评分为<10%和≥10%。以下肿瘤中PD-L1表达≥1%：促性腺激素瘤，21例（28.4%）；促肾上腺皮质激素瘤，5例（6.7%）；促性腺激素/催乳素瘤，2例（2.7%）；无功能性细胞腺瘤，3例（4.0%）；多发性同步垂体神经内分泌肿瘤，2例（2.7%）；未成熟PIT-1肿瘤，1例（1.3%）；成熟PIT-1肿瘤，1例（1.5%）。在以下垂体神经内分泌肿瘤中发现Ki-67≥3%：促性腺激素瘤，3例（4.0%）；促肾上腺皮质激素瘤，2例（2.7%）；催乳素瘤，1例（1.3%）；多发性同步垂体神经内分泌肿瘤，1例（1.3%）；未成熟PIT-1肿瘤，1例（1.3%）；成熟PIT-1肿瘤，1例（1.3%）。Ki-67≥3%的患者在统计学上显著更年轻（P = 0.03）。所有细胞周期蛋白D1≥10%且P53<10%组合的肿瘤在哈代分级中均为侵袭性。在这四个因素中，PD-L1增加侵袭性的几率最高（调整后的OR = 2.35；95%CI：0.56 - 9.90）。PD-L1表达存在于某些类型的垂体神经内分泌肿瘤中。PD-L1表达可能有助于识别无功能性细胞腺瘤。高细胞周期蛋白D1与低P53可能表明肿瘤侵袭性更强。
