28P - Clinical significance of TROP2 expression in lung adenocarcinomas

Background

Trophoblast cell surface antigen 2 (TROP2) is a cell surface glycoprotein expressed in many types of cancers, and its overexpression is associated with poor prognosis. Antibody-drug conjugates that target TROP2 represent a promising approach for the treatment of TROP2-expressing cancers. However, clinical significance of TROP2 expression in lung adenocarcinoma (LUAD) has not been fully elucidated.

Methods

Immunohistochemical (IHC) staining with an anti-TROP2 antibody (SP295) was performed in 1196 surgically resected LUAD tissue microarrays. The intensity of TROP2 expression was scored as 0 (absent), 1 (weak-to-moderate), and 2 (strong). The H-score was defined as the product of the intensity and proportion of positive tumor cells. The positivity of TROP2 expression was evaluated based on the intensity (0 vs. 1/2), proportion of positive tumor cells (<25% vs. ≥25%), and H-score (<50 vs. ≥50). The association of TROP2 overexpression with clinicopathological and molecular characteristics and prognosis was statistically analyzed.

Results

TROP2 overexpression was observed in 916 patients (77%) showing intensity 1/2, 424 (35%) showing positive tumor cells ≥25%, and 268 (22%) showing H-score ≥50. The overall survival of patients with TROP2-positive LUADs was significantly worse than those with TROP2-negative LUADs as the proportion of positive tumor cells or H-score was used as a positive criterion. TROP2 overexpression was significantly associated with men, smoker, advanced pathological stage (stage ≥II), larger tumor size (≥3 cm), lymphatic permeation, vascular invasion, pleural invasion, EGFR wild-type, KRAS mutation, and PD-L1-positive expression.

Conclusions

TROP2 overexpressed LUADs are biologically aggressive tumors and good candidates for TROP2-targetting therapy. The proportion of positive tumor cells and H-score may be useful for patient selection.

Editorial acknowledgement

Clinical trial identification

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.