Department of Pathology, All India Institute of Medical Sciences, New Delhi, India.
Department of Surgical Oncology, Dr BRA Institute-Rotary Cancer Hospital All India Institute of Medical Sciences, New Delhi, 110029, India.
Pathol Oncol Res. 2020 Oct;26(4):2363-2370. doi: 10.1007/s12253-020-00832-0. Epub 2020 Jun 6.
High-grade neuroendocrine tumors (HGNET) have distinctive tumor biology/behaviour. Newer modalities of treatment (immunotherapy) for them have been included in recent NCCN guidelines. Detection of programmed death receptor-ligand 1 (PD-L1) expression by immunohistochemistry have made easy identification of patients eligible for immunotherapy. We aimed to ascertain expression of PD-L1 on small cell and large cell neuroendocrine carcinomas of lung and review existing literature. Eighty-five cases of HGNET lung (primary/metastatic), were retrieved and reviewed. Immunostaining for PD-L1 using clone SP263 was done. Any amount/intensity of membranous staining of > = 1% tumor cells was cut-off for positivity. Previously published studies using Google and/Pubmed search engines were reviewed. Of 85 cases, 70 were small-cell lung cancer (SCLC), 11 large-cell neuroendocrine carcinoma (LCNEC) and 4 combined SCLC. Median age was 46.5 years with male preponderance. No PD-L1 expression was seen in 91.6% cases. The 7 positive cases were 4 LCNEC, 2 SCLC and 1 combined SCLC. The percentage positivity varied from 1-100%; lower percentage positivity was seen in SCLC. PD-L1 expression on immune cells was seen in 31.3% cases. Sixteen studies evaluating 1992 NET were found; E1L3N PD-L1 clone was commonly used clone. PD-L1 positivity was associated with better prognosis in most studies. There are only a few studies available in literature related to PDL1 expression in high grade neuroendocrine carcinomas of lung. In general, PD-L1 positivity is highly variable and seen in lower percentage of these tumors. With the recent approval of immunotherapy, biomarkers other than PD-L1 should also be investigated in these tumors.
高级别神经内分泌肿瘤（HGNET）具有独特的肿瘤生物学/行为。最近的 NCCN 指南中纳入了针对它们的新型治疗方法（免疫疗法）。免疫组化检测程序性死亡受体配体 1（PD-L1）的表达，使得易于识别有资格接受免疫治疗的患者。我们旨在确定 PD-L1 在肺小细胞和大细胞神经内分泌癌中的表达，并回顾现有文献。我们检索并回顾了 85 例 HGNET 肺（原发性/转移性）病例。使用克隆 SP263 进行 PD-L1 免疫染色。将肿瘤细胞膜染色> = 1%的任何数量/强度作为阳性的截断值。使用 Google 和/Pubmed 搜索引擎对以前发表的研究进行了回顾。在 85 例病例中，70 例为小细胞肺癌（SCLC），11 例为大细胞神经内分泌癌（LCNEC），4 例为 SCLC 合并。中位年龄为 46.5 岁，男性居多。91.6%的病例未见 PD-L1 表达。7 例阳性病例分别为 4 例 LCNEC、2 例 SCLC 和 1 例 SCLC 合并。阳性百分比从 1-100%不等；SCLC 的阳性百分比较低。在 31.3%的病例中观察到免疫细胞上的 PD-L1 表达。发现了 16 项评估 1992 年 NET 的研究；E1L3N PD-L1 克隆是常用的克隆。在大多数研究中，PD-L1 阳性与更好的预后相关。文献中仅有少数研究涉及肺高级别神经内分泌癌的 PDL1 表达。总的来说，这些肿瘤中 PD-L1 阳性的比例高度可变，且比例较低。随着免疫治疗的最近批准，这些肿瘤也应该研究其他生物标志物，而不仅仅是 PD-L1。
