Background: Delta-like protein 3 (DLL3) is a Notch ligand that has an important role in the tumorigenesis of small cell lung cancer (SCLC). Recently, rovalpituzumab tesirine (Rova-T), a DLL3-targeted antibody-drug conjugate, has been developed for treating SCLC. DLL3 is a transcriptional target of the achaete-scute homolog-1 (ASCL1) transcription factor, which is involved in pulmonary neuroendocrine cell development. However, the relationship between DLL3 and/or ASCL1 expression and the clinical features of SCLC remains unknown, especially for early-stage resected SCLC. This study aimed to investigate the expression of DLL3 and ASCL1 in resected SCLC samples using immunohistochemical analysis.
Materials and methods: We collected 95 surgically resected SCLC samples, which were formalin fixed and paraffin embedded. Immunohistochemistry staining was performed to investigate the correlation between the expression of either DLL3 or ASCL1 and clinicopathological features of study patients.
Results: Seventy-seven (83%) of 93 immunohistochemically evaluable samples were positive for DLL3 (expression in ≥1% of tumor cells), and DLL3-high expression (≥75%) was observed in 44 samples (47%). Sixty-one (64%) of 95 samples were positive for ASCL1 (expression in ≥5% of tumor cells). A positive correlation was observed between DLL3 and ASCL1 expression. DLL3 and ASCL1 expression were not associated with survival in SCLC patients. DLL3 was more prevalent in patients with advanced clinical disease.
Conclusion: DLL3 and ASCL1 were highly expressed in patients with surgically resected SCLC. DLL3 and ASCL1 may be targets for the treatment of SCLC.
Implications for practice: This article examines the relationship between delta-like protein 3 (DLL3) and achaete-scute homolog-1 (ASCL1) protein expression with the clinical features of 95 surgically resected small cell lung cancer (SCLC). DLL3 is attracting attention because rovalpituzumab tesirine (Rova-T), a DLL3-targeted antibody-drug conjugate, was developed recently. DLL3 and ASCL1 were highly expressed in patients with surgically resected SCLC. DLL3 and ASCL1 may be targets for the treatment of early-stage SCLC, including with Rova-T.
摘要
背景。 δ 样蛋白 3 (DLL3) 是一种 Notch 配体，在小细胞肺癌 (SCLC) 的发生中起着重要作用。近年针对 SCLC 治疗，研制出了一种叫作 rovalpituzumab tesirine (Rova‐T) 的药物，是一种 DLL3 靶向抗体‐药物偶联物。DLL3 是 achaet ‐scute 同源物‐1 (ASCL1) 转录因子的转录靶点，参与肺神经内分泌细胞发育。然而，目前尚不明确 DLL3 和/或 ASCL1 表达与 SCLC 的临床特征之间的关系，尤其是对于早期可切除的 SCLC 患者。本项研究旨在通过免疫组织化学分析方法，研究 DLL3 和 ASCL1 在切除的 SCLC 样本中的表达。
材料和方法。研究选择了 95 例手术切除的 SCLC 标本，标本为福尔马林固定石蜡包埋组织。采用免疫组织化学染色，探讨研究患者的 DLL3 或 ASCL1 表达与临床病理特征的关系。
结果。93 例免疫组化评价标本中，77 例 (83%) 呈 DLL3 阳性(肿瘤细胞表达 ≥1%)，44 例(47%) 呈 DLL3 高表达 (≥75%)。95 个标本中有 61 个 (64%) 呈 ASCL1 阳性(肿瘤细胞表达 ≥5%)。DLL3 与 ASCL1 表达呈正相关。DLL3 和 ASCL1 的表达与 SCLC 患者的生存无关。DLL3 在晚期临床疾病患者中更为常见。
结论。DLL3 和 ASCL1 在手术可切除的 SCLC 患者中高表达。DLL3 和 ASCL1 可能是治疗 SCLC 的靶点。
实践意义:本文结合 95 例手术可切除性小细胞肺癌 (SCLC) 的临床特点，探讨了 δ 样蛋白 3 (DLL3) 与 achaet ‐scute 同源物‐1 (ASCL1) 表达的关系。DLL3 因新研制的一种 DLL3 靶向抗体‐药物偶联物 rovalpituzumab tesirine (Rova‐T) 而备受关注。DLL3 和 ASCL1 在手术可切除的 SCLC 患者中高表达。DLL3 和 ASCL1 可能是治疗早期 SCLC 的靶点，包括 Rova‐T。
Keywords: Achaete‐scute homolog‐1; Delta‐like protein 3; Immunohistochemistry; Small cell lung cancer; Surgery.
© AlphaMed Press 2019.