Expressão de DLL3 e ASCL1 e sua relação com aspectos clínico-patológicos no carcinoma de pequenas células do pulmão

Abstract

Small cell lung carcinoma (SCLC) is a cancer subtype characterized by the presence of small cells with a neuroendocrine phenotype. It accounts for 15% of lung tumors and becomes a very challenging disease due to therapeutic limitations and poor prognosis with a short survival time. In recent years, the activity of the protein acetate scute homologue 1 (ASCL1) has been identified as a neuroendocrine regulator associated with the progression of SCLC. The activity of the protein Delta Like Ligand 3 (DLL3) has also been observed as a regulator of the Notch protein, which has a tumor suppressor role. Clinical studies were then developed with pharmacological inhibitors that target DLL3, leading in 2024 to the approval of Tarlatamab, which targets DLL3 and CD3 lymphocytes. The present study sought to evaluate the expression of DLL3 and ASCL1 and correlate with other neuroendocrine proteins of SCLC, as well as survival. A retrospective cross-sectional cohort study was conducted with 84 cases diagnosed with SCLC in Fortaleza-CE. Immunohistochemistry (IHC) for DLL3, ASCL1, TTF1 and KI67 was performed on the paraffin blocks of the patients included in the study. The slides were scanned and evaluated using QuPath software. Statistical analyses of association with Student's t-test, correlation with Pearson's test, survival assessment by log-rank and multivariate analysis with COX logistic regression were performed based on the results and clinical-pathological data obtained. In the study, an association was identified between TTF1 proteins with DLL3 and ASCL1, indicating that patients with higher positivity for TTF1 had higher expression of DLL3 and ASCL1. A statistical correlation was also observed between TTF1 and DLL3 and the relationship between ASCL1 and survival, with cases negative for ASCL1 having lower survival. The present study is a pioneering study in the evaluation of DLL3 and ASCL1 in the region, and the high positivity of these proteins indicates a new therapeutic possibility for patients in Ceará, in addition to generating a new perspective on the complex carcinogenic mechanism of SCLC.