In patients with small cell lung cancer, DLL3 relationship with prognosis, clinical parameters and treatment response

Introduction: SCLC is associated with limited treatment options and poor prognosis. A notch signaling pathway inhibitory DLL3 was shown to be expressed in SCLC. In normal lung parenchyma and non-malignant cells, DLL3 was found to be slightly possitive, this finding makes DLL3 a potential target. Purpose: We aimed to show expression level of DLL3 by immunohistochemical staining and its relationship with other clinical parameters and disease prognosis in SCLC patients. Methods: Sixty patients who apply to Akdeniz Unıversity Medical Oncology Department between January 2008 and October 2017 and diagnosed with extensive or limited SCLC in primary or metastatic tissue sample were included in this study. The patients with pathology preparations which could be reached at Akdeniz University Medical Pathology Department and had been enough cells for staining were selected. Their pathology preparations at the time of diagnosis were examined. Clinical data of patients was obtained from computer system and patients files retrospectively. Findings: DLL3 staining intensity, in %15 of patients were 0, in %45 of patients were 1, in %26,7 of patients were 2 and in %13,3 of patients were 3. Number of patients with DLL3 staining percentage <1 were 9 (%15), 1-49 were 15 (%25) and ≥50 were 36 (%60). DLL3 staining status, percentage and intensity and patients clinical parameters (ages of patients, gender distributions, disease stages, smoking situation, responses to first line chemotherapy treatment, ECOG performance status, how many lines of chemotherapy they take, central nervous system metastasis at diagnosis) were evoluated. There was no relationship between these clinical parameters and DLL3 expression levels. It was determined that patients with lower DLL3 staining percentage (<50) had longer survival than patients with high DLL3 staining percentage (≥50). When the DLL3 staining intensity was evaluated, the lowest survival rates were seen in patients with DLL3 staining intensity 3. When only patients with extensive stage disease were evaluated, the findings were similar. Negative correlation between DLL3 and survival time was shown. Conclusion: While there was no relationship between the intensity and percentage of DLL3 staining and clinical parameters, there was a negative correlation between survival time and DLL3 staining level in both groups and pantients with extensive stage disease. This finding suggests that DLL3 and disease prognosis may be related. Keywords: small cell lung cancer, delta-like protein 3, prognosis, survivaltime