WCLC 2025 - Posters & ePosters-P2.06.25 Clinical Implications of TROP2 Expression in Lung Adenocarcinomas

Pdf Summary

This study investigated the clinical significance of Trophoblast cell surface antigen 2 (TROP2) expression in lung adenocarcinomas (LUAD). TROP2, a glycoprotein overexpressed in many cancers, is linked to poor prognosis and is a target for antibody-drug conjugates (ADCs). However, traditional immunohistochemistry (IHC) scoring has not reliably predicted responses to TROP2-directed ADCs in non-small cell lung cancer (NSCLC). Additionally, TROP2 overexpression has been associated with worse outcomes following PD-L1 blockade therapy and gefitinib resistance in EGFR-mutated lung cancers, but its role in LUAD had not been fully elucidated.<br /><br />Using IHC staining for TROP2 on 1,067 surgically resected LUAD samples, the study assessed TROP2 positivity by intensity (0=absent, 1=weak/moderate, 2=strong), proportion of positive tumor cells, and an H-score combining intensity and proportion. Statistical analyses correlated TROP2 expression with clinicopathological, molecular features, and survival outcomes.<br /><br />Results showed that high TROP2 expression (particularly measured by H-score >50) was significantly associated with more aggressive clinical features, including advanced pathological stage, larger tumor size, elevated serum CEA, and histological high-grade subtypes. TROP2 overexpression correlated with mutations in EGFR and KRAS, as well as PD-L1 positivity. Multivariate analyses identified established factors such as age, sex, serum CEA, advanced stage, lymphatic and vascular invasion as significant prognostic factors, but TROP2 overexpression was not an independent prognostic factor overall. Furthermore, in PD-L1 positive and EGFR mutated LUAD subsets, TROP2 expression did not significantly affect overall or relapse-free survival.<br /><br />The study concluded that LUADs with high TROP2 expression constitute biologically aggressive tumors and represent good candidates for TROP2-targeted therapies. Among evaluation methods, the H-score was the most effective for reflecting tumor aggressiveness. However, TROP2 expression lacks prognostic value in PD-L1 positive and EGFR mutated LUAD subgroups.

Asset Subtitle

Kazuya Takamochi

Meta Tag

Speaker Kazuya Takamochi

Topic Pathology and Biomarkers

Keywords

TROP2

lung adenocarcinoma

LUAD

immunohistochemistry

H-score

EGFR mutation

PD-L1 positivity

tumor aggressiveness

antibody-drug conjugates

prognostic factors