Expression of delta-like protein 3 is reproducibly present in a subset of small cell lung carcinomas and pulmonary carcinoid tumors. (September 2019)

• Record Type: Journal Article
• Authors: Xie, Hao; Boland, Jennifer M.; Maleszewski, Joseph J.; Aubry, Marie Christine; Yi, Eunhee S.; Jenkins, Sarah M.; Koepplin, Justin W.; Terra, Simone B S P; Mansfield, Aaron S.; Roden, Anja C.
• Is Part Of: Lung cancer. Volume 135(2019)
• Page Start: 73
• Page End: 79
• Publication Date: 2019-09
• Subjects: Carcinoid tumors -- Small cell lung cancer -- DLL3 -- Rovalpituzumab tesirine; Lungs -- Cancer -- Periodicals; Lung Neoplasms -- Abstracts; Lung Neoplasms -- Periodicals; Poumons -- Cancer -- Périodiques; Lungs -- Cancer; Periodicals; Electronic journals; Electronic journals; 616.99424
• DOI: 10.1016/j.lungcan.2019.07.016
• Languages: English
• ISSNs: 0169-5002

Abstract

Highlights: Interobserver agreement for DLL3 expression is substantial among thoracic pathologists. High DLL3 expression (≥ 50% of tumor cells) is observed in almost 80% of small cell lung carcinomas. Approximately one third of atypical and typical carcinoid tumors show high DLL3 expression. High DLL3 expression is associated with better overall survival in small cell lung carcinomas. Abstract: Objectives: Delta-like protein 3 (DLL3), an inhibitory Notch ligand, is the target for rovalpituzumab tesirine in development for the treatment of small cell lung cancer (SCLC). We studied the expression of DLL3, its reproducibility and prognostic role in pulmonary neuroendocrine tumors. Materials and Methods: Institutional pathology files were searched for resected pulmonary neuroendocrine tumors (1995–2017). Expression of DLL3 (clone SP347) was categorized as high (≥50% of tumor cells) or low (<50%). Interobserver agreement among 5 thoracic pathologists was measured by Krippendorff's α coefficient. Staging (N = 148) was performed according to the 8th AJCC. Results: Our study included 157 patients with a median age of 62.2 years (range 23.2–88.1) including 59 men (37.6%). Tumors included 44 (28.0%) SCLC, 46 (29.3%) atypical and 67 (42.7%) typical carcinoid tumors at stages I (N = 83, 56.1%), II (N = 28, 18.9%), and III/IV (N = 37, 25.0%). Interobserver agreement for high vs low DLL3 expression (N = 70) was 82.9% (α = 0.79, substantial). High DLL3 expression was observed in 35 (79.5%) SCLC, 17 (37.0%) atypical and 22 (32.8%) typical carcinoid tumors. High DLL3 was associated with SCLC morphology (p < 0.0001). During a median follow-up of 4.2 years (range, 2 days–20.3 years), 70 patients died; 19 died from disease. High DLL3 expression was associated with better overall survival in SCLC (p = 0.049) but not after adjusting for age, tumor size and stage. Conclusions: DLL3 expression is reliably quantifiable by pathologists and is highly expressed in the majority of SCLC and a subset of carcinoid tumors, making it an attractive target for anti-DLL3 treatment.