title: Association of tumor TROP2 expression with prognosis varies among lung cancer subtypes.
abstract: TROP2 is a transmembrane glycoprotein that is overexpressed in various cancers. Emerging evidence suggests that TROP2-targeting therapies are efficacious and safe in patients with multiple prior treatments. TROP2 is a promising target for lung cancer treatment; however, little is known regarding the association of TROP2 expression with clinicopathological/molecular features, including prognosis, in lung cancer. We examined consecutive cases of adenocarcinoma, squamous cell carcinoma (SqCC), and high-grade neuroendocrine tumor (HGNET) for the membranous expression of TROP2 using immunohistochemistry. High TROP2 expression was observed in 64% (172/270) of adenocarcinomas, 75% (150/201) of SqCCs, and 18% (21/115) of HGNETs. Intriguingly, the association of TROP2 expression with mortality was dependent on the lung cancer subtype. High TROP2 expression was associated with higher lung cancer-specific mortality in adenocarcinomas [univariable hazard ratio (HR) = 1.60, 95% confidence interval (CI) = 1.07-2.44, P = 0.022)], but not in SqCCs (univariable HR = 0.79, 95% CI = 0.35-1.94, P = 0.79). In HGNETs, high TROP2 expression was associated with lower lung cancer-specific mortality in both univariable and multivariable analyses (multivariable HR = 0.13, 95% CI = 0.020-0.44, P = 0.0003). Our results suggest a differential role for TROP2 in different lung cancer subtypes.
authors.affiliation: Division of Pathology, The Cancer Institute; Department of Pathology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Koto-ku, Tokyo 135-8550, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Inamura
authors.affiliation: Translational Medicine & Clinical Pharmacology Department, Daiichi Sankyo Co., Ltd., Shinagawa-ku, Tokyo 140-0005, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Yokouchi
authors.affiliation: Division of Pathology, The Cancer Institute; Department of Pathology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Koto-ku, Tokyo 135-8550, Japan.
authors.forename: Maki
authors.initials: M
authors.lastname: Kobayashi
authors.affiliation: Division of Pathology, The Cancer Institute; Department of Pathology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Koto-ku, Tokyo 135-8550, Japan.
authors.forename: Hironori
authors.initials: H
authors.lastname: Ninomiya
authors.affiliation: Division of Pathology, The Cancer Institute; Department of Pathology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Koto-ku, Tokyo 135-8550, Japan.|Department of Integrated Pulmonology, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8519, Japan.
authors.forename: Rie
authors.initials: R
authors.lastname: Sakakibara
authors.affiliation: Division of Pathology, The Cancer Institute; Department of Pathology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Koto-ku, Tokyo 135-8550, Japan.
authors.forename: Sophia
authors.initials: S
authors.lastname: Subat
authors.affiliation: Division of Pathology, The Cancer Institute; Department of Pathology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Koto-ku, Tokyo 135-8550, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Nagano
authors.affiliation: Division of Pathology, The Cancer Institute; Department of Pathology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Koto-ku, Tokyo 135-8550, Japan.
authors.forename: Kimie
authors.initials: K
authors.lastname: Nomura
authors.affiliation: Thoracic Oncology Center, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Koto-ku, Tokyo 135-8550, Japan.
authors.forename: Sakae
authors.initials: S
authors.lastname: Okumura
authors.affiliation: Translational Medicine & Clinical Pharmacology Department, Daiichi Sankyo Co., Ltd., Shinagawa-ku, Tokyo 140-0005, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Shibutani
authors.affiliation: Division of Pathology, The Cancer Institute; Department of Pathology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Koto-ku, Tokyo 135-8550, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Ishikawa
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D018358:Neuroendocrine Tumors / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality; D011379:Prognosis; D016019:Survival Analysis; D015854:Up-Regulation
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D015815:Cell Adhesion Molecules; C499380:TACSTD2 protein, human
keywords: TROP2; antibody-drug conjugate; lung cancer; molecular targeted therapy; outcome