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Analysis of DLL3 and ASCL1 in Surgically Resected Small Cell Lung Cancer (HOT1702)

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Please use this identifier to cite or link to this item:http://hdl.handle.net/2115/77804

Title: Analysis of DLL3 and ASCL1 in Surgically Resected Small Cell Lung Cancer (HOT1702)
Authors: Furuta, Megumi Browse this author →KAKEN DB
Sakakibara-Konishi, Jun Browse this author →KAKEN DB
Kikuchi, Hajime Browse this author
Yokouchi, Hiroshi Browse this author →KAKEN DB
Nishihara, Hiroshi Browse this author →KAKEN DB
Minemura, Hiroyuki Browse this author
Harada, Masao Browse this author
Yamazaki, Shigeo Browse this author
Akie, Kenji Browse this author
Fujita, Yuka Browse this author
Takamura, Kei Browse this author
Kojima, Tetsuya Browse this author
Harada, Toshiyuki Browse this author
Minami, Yoshinori Browse this author →KAKEN DB
Watanabe, Naomi Browse this author
Oizumi, Satoshi Browse this author →KAKEN DB
Suzuki, Hiroyuki Browse this author →KAKEN DB
Nishimura, Masaharu Browse this author →KAKEN DB
Dosaka-Akita, Hirotoshi Browse this author →KAKEN DB
Isobe, Hiroshi Browse this author →KAKEN DB
Keywords: Small cell lung cancer
Delta-like protein 3
Achaete-scute homolog-1
Immunohistochemistry
Surgery
Issue Date: Nov-2019
Publisher: John Wiley & Sons
Journal Title: The Oncologist
Volume: 24
Issue: 11
Start Page: E1172
End Page: E1179
Publisher DOI: 10.1634/theoncologist.2018-0676
Abstract: Background Delta-like protein 3 (DLL3) is a Notch ligand that has an important role in the tumorigenesis of small cell lung cancer (SCLC). Recently, rovalpituzumab tesirine (Rova-T), a DLL3-targeted antibody-drug conjugate, has been developed for treating SCLC. DLL3 is a transcriptional target of the achaete-scute homolog-1 (ASCL1) transcription factor, which is involved in pulmonary neuroendocrine cell development. However, the relationship between DLL3 and/or ASCL1 expression and the clinical features of SCLC remains unknown, especially for early-stage resected SCLC. This study aimed to investigate the expression of DLL3 and ASCL1 in resected SCLC samples using immunohistochemical analysis. Materials and Methods We collected 95 surgically resected SCLC samples, which were formalin fixed and paraffin embedded. Immunohistochemistry staining was performed to investigate the correlation between the expression of either DLL3 or ASCL1 and clinicopathological features of study patients. Results Seventy-seven (83%) of 93 immunohistochemically evaluable samples were positive for DLL3 (expression in >= 1% of tumor cells), and DLL3-high expression (>= 75%) was observed in 44 samples (47%). Sixty-one (64%) of 95 samples were positive for ASCL1 (expression in >= 5% of tumor cells). A positive correlation was observed between DLL3 and ASCL1 expression. DLL3 and ASCL1 expression were not associated with survival in SCLC patients. DLL3 was more prevalent in patients with advanced clinical disease. Conclusion DLL3 and ASCL1 were highly expressed in patients with surgically resected SCLC. DLL3 and ASCL1 may be targets for the treatment of SCLC. Implications for Practice This article examines the relationship between delta-like protein 3 (DLL3) and achaete-scute homolog-1 (ASCL1) protein expression with the clinical features of 95 surgically resected small cell lung cancer (SCLC). DLL3 is attracting attention because rovalpituzumab tesirine (Rova-T), a DLL3-targeted antibody-drug conjugate, was developed recently. DLL3 and ASCL1 were highly expressed in patients with surgically resected SCLC. DLL3 and ASCL1 may be targets for the treatment of early-stage SCLC, including with Rova-T.
Type: article (author version)
URI: http://hdl.handle.net/2115/77804
Appears in Collections:医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 榊原 純

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