Association of tumor TROP2 expression with prognosis varies among lung cancer subtypes
// Kentaro Inamura 1 , Yusuke Yokouchi 2 , Maki Kobayashi 1 , Hironori Ninomiya 1 , Rie Sakakibara 1, 3 , Sophia Subat 1 , Hiroko Nagano 1 , Kimie Nomura 1 , Sakae Okumura 4 , Tomoko Shibutani 2 , Yuichi Ishikawa 1 1 Division of Pathology, The Cancer Institute, Department of Pathology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Koto-ku, Tokyo 135-8550, Japan 2 Translational Medicine & Clinical Pharmacology Department, Daiichi Sankyo Co., Ltd., Shinagawa-ku, Tokyo 140-0005, Japan 3 Department of Integrated Pulmonology, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8519, Japan 4 Thoracic 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.