Anatomical Pathology, Douglass Hanly Moir Pathology, 14 Giffnock Avenue, Macquarie Park, NSW, 2113, Australia.
Discipline of Pathology, MQ Health, Macquarie University, Macquarie Park, NSW, 2113, Australia.
Endocr Pathol. 2021 Sep;32(3):408-414. doi: 10.1007/s12022-021-09673-2. Epub 2021 Mar 11.
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.
垂体神经内分泌肿瘤（PitNETs）会导致终生发病，部分患者需要进行广泛的手术干预、放疗或化疗。一小部分患者仍患有进行性疾病，对标准治疗耐药，可能受益于新的治疗方法。我们评估了大量 PitNETs 中的 PD-L1 表达，以探讨免疫疗法是否可作为合理的治疗选择。根据世界卫生组织 2017 年的系统，对接受手术切除的未选择的 PitNETs 进行重新分类，并在组织微阵列格式中进行 PD-L1 免疫组化（克隆 SP263）。膜表达评分 0（无表达）、1+（<50%表达）和 2+（>50%表达）。共 265 例 PitNETs 进行了 PD-L1 免疫组化。由于显著的非特异性细胞质染色，使得真正的膜表达评估变得困难。考虑到这一点，264 例中的 40 例（15%） PitNETs 显示出强染色（>50%的肿瘤细胞阳性）。其中包括 5/10（50%）生长激素细胞瘤、7/17（41%）催乳素细胞瘤、2/5（40%）哺乳-生长激素细胞瘤、4/8（50%）混合生长激素-催乳素细胞瘤、3/5（60%）表达 TSH 的 PIT-1 阳性多激素肿瘤、28 例 PIT-1 阳性多激素肿瘤中的 10 例（36%）和 10 例 PIT-1 阳性无激素表达的肿瘤中的 4 例（40%）。仅 2/32（6%）转录因子三阴性、激素阴性肿瘤、113 例促性腺激素中的 5 例（4%）、0/6 例促甲状腺激素细胞瘤或 0/30 例促肾上腺皮质激素细胞瘤显示出显著染色。我们的结论是，PD-L1 表达在生长激素细胞瘤、催乳素细胞瘤和 PIT-1 阳性多激素 PitNETs 中常见，但在转录因子阴性、激素阴性 PitNETs、促性腺激素和促肾上腺皮质激素细胞瘤中罕见。如果要在 PitNETs 中探索免疫疗法的治疗作用，那么它可能对 PD-L1 高亚组最有益。
