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PD-L1 Is Preferentially Expressed in PIT-1 Positive Pituitary Neuroendocrine Tumours
Endocrine Pathology ( IF 4.4 ) Pub Date : 2021-03-11 , DOI: 10.1007/s12022-021-09673-2
John Turchini 1, 2, 3, 4 , Loretta Sioson 4 , Adele Clarkson 4, 5 , Amy Sheen 4 , Anthony J Gill 3, 4, 5
Affiliation  

Pituitary neuroendocrine tumours (PitNETs) cause lifelong morbidity, some requiring extensive surgical intervention, radiotherapy, or chemotherapy. A small percentage still cause debilitating disease, resistant to standard treatments, and may benefit from novel therapies. We assessed PD-L1 expression in a large cohort of PitNETs to investigate whether immunotherapy could represent a rational therapeutic choice. Unselected PitNETs undergoing surgical resection were reclassified according to the WHO 2017 system and underwent PD-L1 immunohistochemistry (clone SP263) in tissue microarray format. Membranous expression was scored as 0 (no expression), 1+ (< 50% expression) and 2+ (> 50% expression). A total of 265 PitNETs underwent PD-L1 immunohistochemistry. Prominent non-specific cytoplasmic staining was noted making assessment of true membrane expression difficult. Allowing for this, 40 of 264 (15%) PitNETs demonstrated strong staining (> 50% of neoplastic cells positive). These included 5/10 (50%) somatotrophs, 7/17 (41%) lactotrophs, 2/5 (40%) mammosomatotrophs, 4/8 (50%) mixed somatotroph-lactotrophs, 3/5 (60%) PIT-1 positive plurihormonal tumours with TSH expression, 10/28 (36%) of PIT-1 positive plurihormonal tumours, and 4/10 (40%) of PIT-1 positive tumours with no hormonal expression. Only 2/32 (6%) transcription factor triple negative, hormone negative tumours, 5/113 (4%) of gonadotrophs, and 0/6 thyrotrophs or 0/30 corticotrophs showed significant staining. We conclude that PD-L1 expression is common in somatotrophs, lactotrophs, and PIT-1 positive plurihormonal PitNETs but rare in transcription factor negative, hormone negative PitNETs, gonadotrophs, and corticotrophs. If the therapeutic role of immunotherapy is to be explored in PitNETs, it may be that it is of most benefit in the PD-L1 high subgroup.



中文翻译:

PD-L1 在 PIT-1 阳性垂体神经内分泌肿瘤中优先表达

垂体神经内分泌肿瘤 (PitNETs) 会导致终生发病,其中一些需要广泛的手术干预、放疗或化疗。一小部分仍然会导致使人衰弱的疾病,对标准治疗有抵抗力,并且可能会受益于新疗法。我们在一大群 PitNETs 中评估了 PD-L1 的表达,以研究免疫疗法是否可以代表一种合理的治疗选择。根据 WHO 2017 系统对未选择的接受手术切除的 PitNET 进行重新分类,并以组织微阵列格式接受 PD-L1 免疫组织化学(克隆 SP263)。膜表达评分为 0(无表达)、1+(< 50% 表达)和 2+(> 50% 表达)。共有 265 个 PitNETs 接受了 PD-L1 免疫组化。注意到突出的非特异性细胞质染色使得评估真正的膜表达变得困难。考虑到这一点,264 个 PitNET 中有 40 个(15%)表现出强染色(> 50% 的肿瘤细胞呈阳性)。这些包括 5/10 (50%) 生长激素、7/17 (41%) 泌乳素、2/5 (40%) 乳腺生长素、4/8 (50%) 混合生长素-泌乳素、3/5 (60%) PIT- 1 阳性多激素肿瘤有 TSH 表达,10/28 (36%) PIT-1 阳性多激素肿瘤和 4/10 (40%) PIT-1 阳性肿瘤无激素表达。只有 2/32 (6%) 转录因子三阴性、激素阴性肿瘤、5/113 (4%) 促性腺激素和 0/6 促甲状腺激素或 0/30 促肾上腺皮质激素显示显着染色。我们得出结论,PD-L1 表达在生长激素、泌乳素、和 PIT-1 阳性多激素 PitNET,但在转录因子阴性、激素阴性 PitNET、促性腺激素和促肾上腺皮质激素中很少见。如果要在 PitNETs 中探索免疫疗法的治疗作用,它可能对 PD-L1 高亚组最有益。

更新日期:2021-03-11
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