Non-small cell lung cancer: a comparative analysis of methods for assessing TROP2 expression in relation to clinical and morphological characteristics

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.