Oncotarget

Research Papers:

Association of tumor TROP2 expression with prognosis varies among lung cancer subtypes

Kentaro Inamura, Yusuke Yokouchi, Maki Kobayashi, Hironori Ninomiya, Rie Sakakibara, Sophia Subat, Hiroko Nagano, Kimie Nomura, Sakae Okumura, Tomoko Shibutani and Yuichi Ishikawa _

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Oncotarget. 2017; 8:28725-28735. https://doi.org/10.18632/oncotarget.15647

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Abstract

Kentaro Inamura1, Yusuke Yokouchi2, Maki Kobayashi1, Hironori Ninomiya1, Rie Sakakibara1,3, Sophia Subat1, Hiroko Nagano1, Kimie Nomura1, Sakae Okumura4, Tomoko Shibutani2, Yuichi Ishikawa1

1Division of Pathology, The Cancer Institute, Department of Pathology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Koto-ku, Tokyo 135-8550, Japan

2Translational Medicine & Clinical Pharmacology Department, Daiichi Sankyo Co., Ltd., Shinagawa-ku, Tokyo 140-0005, Japan

3Department of Integrated Pulmonology, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8519, Japan

4Thoracic Oncology Center, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Koto-ku, Tokyo 135-8550, Japan

Correspondence to:

Yuichi Ishikawa, email: ishikawa@jfcr.or.jp

Keywords: antibody-drug conjugate, lung cancer, molecular targeted therapy, outcome, TROP2

Received: October 07, 2016    Accepted: January 27, 2017    Published: February 23, 2017

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.


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