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.
Highlights
TROP2 is a transmembrane glycoprotein that has high expression in many cancers and is associated with patient survival [1,2,3,4,5,6,7,8,9,10,11]
Because TROP2 is a promising molecular target for the treatment of lung cancer, we examined the association of TROP2 expression with clinicopathological and molecular features as well as with prognosis of various lung cancer subtypes, including 270 consecutive cases of adenocarcinoma, 201 cases of squamous cell carcinoma (SqCC), and 115 cases of high-grade neuroendocrine tumor (HGNET) (74 cases of small cell lung carcinoma (SCLC) and 41 cases of large www.impactjournals.com/oncotarget cell neuroendocrine carcinoma (LCNEC))
We examined the association of TROP2 expression in tumors with clinicopathological/molecular features and with prognosis of various lung cancer subtypes, including adenocarcinoma, SqCC, and HGNET (SCLC and LCNEC)
Summary
TROP2 ( known as TACSTD2) is a transmembrane glycoprotein that has high expression in many cancers and is associated with patient survival [1,2,3,4,5,6,7,8,9,10,11]. TROP2 has been used as a target of antibody-drug conjugate (ADC) therapy [11]. Sacituzumab govitecan (IMMU-132) is an anti-TROP2 ADC [11,12,13,14,15,16,17,18] that contains SN-38, the active metabolite of irinotecan. IMMU-132 has been effective against triple-negative breast cancer [19], metastatic small cell lung carcinoma (SCLC) [14], and metastatic non-SCLC (NSCLC) resistant to anti-PD-1/PD-L1 therapy [15]
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