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Updated: Oct 17, 2026
Ultra-Fast Amplicon-Based Next-Generation Sequencing in Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
[Non-small cell lung cancer: a comparative analysis of methods for assessing TROP2 expression in relation to clinical
S V Vtorushin1,2, D M Loos1, L A Tashireva1
1Cancer Research Institute - Tomsk National Research Medical Center, Tomsk, Russia.
Abstract:
Trophoblast cell surface antigen 2 (TROP2) has emerged as a promising therapeutic target in non-small cell lung cancer (NSCLC) in the context of the development of antibody-drug conjugates. In this setting, reproducible and biologically meaningful immunohistochemical assessment of TROP2 expression, taking into account its intracellular localization, is of particular importance.
Objective:
To characterize TROP2 expression in lung adenocarcinomas and squamous cell carcinomas and to evaluate its association with clinicopathological parameters using different immunohistochemical assessment methods.
Material And Methods:
This retrospective single-center study included 60 cases of NSCLC (30 adenocarcinomas and 30 squamous cell carcinomas) diagnosed between 2019 and 2023. TROP2 expression was evaluated by immunohistochemistry using the semi-quantitative H-score and the normalized membrane ratio (NMR), reflecting the relative contribution of membranous and cytoplasmic expression. Associations between TROP2 expression and clinicopathological characteristics were analyzed.
Results:
TROP2 expression was detected in all examined NSCLC samples. TROP2 expression assessed by H-score was significantly higher in squamous cell carcinoma compared with lung adenocarcinoma (p=0.0001), whereas NMR values did not differ between histological subtypes. No associations were observed between H-score and clinicopathological parameters. In contrast, NMR demonstrated histotype-dependent associations: with tumor stage in lung adenocarcinoma (p=0.0483) and with lymphovascular invasion in squamous cell carcinoma (p=0.0139). The proportion of cases meeting the NMR-based criteria for TROP2 positivity was low.
Conclusion:
The results indicate that the choice of TROP2 assessment method substantially influences data interpretation. Consideration of intracellular protein localization using the NMR appears to be more informative than conventional semi-quantitative approaches and may reflect biological features of tumor progression in NSCLC.