Oncotarget

Research Papers:

Relationship between the expressions of DLL3, ASC1, TTF-1 and Ki-67: First steps of precision medicine at SCLC

Samuel Silva, Juliana C. Sousa, Cleto Nogueira, Raquel Feijo, Francisco Martins Neto, Laura Cardoso Marinho, Guilherme Sousa, Valeria Denninghoff and Fabio Tavora _

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Oncotarget. 2024; 15:750-763. https://doi.org/10.18632/oncotarget.28660

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Abstract

Samuel Silva1,2, Juliana C. Sousa2, Cleto Nogueira1,2, Raquel Feijo1,3, Francisco Martins Neto3, Laura Cardoso Marinho1,2, Guilherme Sousa2, Valeria Denninghoff4,5 and Fabio Tavora1,2

1 Department of Pathology, Faculty of Medicine, Federal University of Ceará, Fortaleza (Ceará), Brazil

2 ARGOS Laboratory, Fortaleza (Ceará), Brazil

3 Messejana Heart and Lung Hospital, Fortaleza (Ceará), Brazil

4 Molecular Oncology Clinical Lab, University of Buenos Aires (UBA)—National Council for Scientific and Technical Research (CONICET), Buenos Aires, Argentina

5 Liquid Biopsy and Cancer Interception Unit, GENYO, Centre for Genomics and Oncological Research (Pfizer/University of Granada/Andalusian Regional Government), Granada, Spain

Correspondence to:

Fabio Tavora, email: [email protected]

Keywords: DLL3; pathology; biomarkers; qupath; small cell carcinoma

Received: July 29, 2024     Accepted: September 17, 2024     Published: October 11, 2024

Copyright: © 2024 Silva et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

ABSTRACT

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.


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