Department of Pathology, Faculty of Medicine, Federal University of Ceará, Fortaleza (Ceará), Brazil.
ARGOS Laboratory, Fortaleza (Ceará), Brazil.
Oncotarget. 2024 Oct 11;15:750-763. doi: 10.18632/oncotarget.28660.
This study presents an observational, cross-sectional analysis of 64 patients diagnosed with small cell lung cancer (SCLC) at a reference laboratory for thoracic pathology between 2022 and 2024. The primary objective was to evaluate the expression of Delta-like ligand 3 (DLL3) and other neuroendocrine markers such as Chromogranin, and Synaptophysin, utilizing both traditional immunohistochemistry and digital pathology tools. Patients were primarily older adults, with a median age of over 71, and most biopsies were obtained from lung parenchyma. Immunohistochemistry (IHC) was performed using specific monoclonal antibodies, with DLL3 showing variable expression across the samples. Notably, DLL3 was expressed in 72.3% of the cases, with varied intensities and a semi-quantitative H-score applied for more nuanced analysis. ASCL1 was expressed in 97% of cases, with the majority considered low-expressors. Only 11% had high expression. TTF-1, traditionally not a conventional marker for the diagnosis of SCLC, was positive in half of the cases, suggesting its potential as a biomarker. The study underscores the significant variability in the expression of neuroendocrine markers in SCLC, with implications for both diagnosis and potential therapeutic targeting. DLL3, particularly, shows promise as a therapeutic target due to its high expression rate in the cohort. The use of digital pathology software QuPath enhanced the accuracy and depth of analysis, allowing for detailed morphometric analysis and potentially informing more personalized treatment approaches. The findings emphasize the need for further research into the role of these markers in the management and treatment of SCLC, considering the poor prognosis and high mortality rate observed in the cohort.
本研究对 2022 年至 2024 年间在胸病理参考实验室诊断为小细胞肺癌 (SCLC) 的 64 例患者进行了观察性、横断面分析。主要目的是评估 Delta-like ligand 3 (DLL3) 及其他神经内分泌标志物（如 Chromogranin 和 Synaptophysin）的表达，利用传统免疫组织化学和数字病理学工具。患者主要为老年人，中位年龄超过 71 岁，大多数活检均来自肺实质。免疫组织化学（IHC）使用特定的单克隆抗体进行，DLL3 在样本中表现出不同程度的表达。值得注意的是，DLL3 在 72.3%的病例中表达，其强度不同，并应用半定量 H 评分进行更细致的分析。ASCL1 在 97%的病例中表达，大多数被认为是低表达者，只有 11%有高表达。TTF-1 传统上不是 SCLC 诊断的常规标志物，但在半数病例中呈阳性，表明其作为生物标志物的潜力。研究强调了 SCLC 中神经内分泌标志物表达的显著变异性，对诊断和潜在的治疗靶向均具有重要意义。DLL3 由于在该队列中表达率较高，因此作为治疗靶点具有很大的潜力。数字病理学软件 QuPath 的使用提高了分析的准确性和深度，允许进行详细的形态计量分析，并可能为更个性化的治疗方法提供信息。这些发现强调了需要进一步研究这些标志物在 SCLC 管理和治疗中的作用，考虑到该队列中观察到的预后不良和高死亡率。
