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

Hao Xie, Jennifer M. Boland, Joseph Maleszewski, Marie Christine Aubry, Eunhee S. Yi, Sarah M. Jenkins, Justin W. Koepplin, Simone B.S.P. Terra, Aaron Mansfield, Anja Roden

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)73-79
Number of pages7
JournalLung Cancer
Volume135
DOIs
StatePublished - Sep 1 2019

Fingerprint

Small Cell Lung Carcinoma
Carcinoid Tumor
Lung
Neuroendocrine Tumors
delta protein
Neoplasms
Thorax
Clone Cells
Pathology
Ligands
Survival
Therapeutics

Keywords

  • Carcinoid tumors
  • DLL3
  • Rovalpituzumab tesirine
  • Small cell lung cancer

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Cancer Research

Cite this

Expression of delta-like protein 3 is reproducibly present in a subset of small cell lung carcinomas and pulmonary carcinoid tumors. / Xie, Hao; Boland, Jennifer M.; Maleszewski, Joseph; Aubry, Marie Christine; Yi, Eunhee S.; Jenkins, Sarah M.; Koepplin, Justin W.; Terra, Simone B.S.P.; Mansfield, Aaron; Roden, Anja.

In: Lung Cancer, Vol. 135, 01.09.2019, p. 73-79.

Research output: Contribution to journalArticle

Xie, Hao ; Boland, Jennifer M. ; Maleszewski, Joseph ; Aubry, Marie Christine ; Yi, Eunhee S. ; Jenkins, Sarah M. ; Koepplin, Justin W. ; Terra, Simone B.S.P. ; Mansfield, Aaron ; Roden, Anja. / Expression of delta-like protein 3 is reproducibly present in a subset of small cell lung carcinomas and pulmonary carcinoid tumors. In: Lung Cancer. 2019 ; Vol. 135. pp. 73-79.
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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.",
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T1 - Expression of delta-like protein 3 is reproducibly present in a subset of small cell lung carcinomas and pulmonary carcinoid tumors

AU - Xie, Hao

AU - Boland, Jennifer M.

AU - Maleszewski, Joseph

AU - Aubry, Marie Christine

AU - Yi, Eunhee S.

AU - Jenkins, Sarah M.

AU - Koepplin, Justin W.

AU - Terra, Simone B.S.P.

AU - Mansfield, Aaron

AU - Roden, Anja

PY - 2019/9/1

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N2 - 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.

AB - 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.

KW - Carcinoid tumors

KW - DLL3

KW - Rovalpituzumab tesirine

KW - Small cell lung cancer

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