The relationship between TROP2 expression status and clinicopathological parameters in non-small cell lung carcinomas

Aim: Lung cancer continues to represent a major global public health challenge, characterized by high incidence rates and ranking as a leading cause of cancer related mortality worldwide. Therefore new molecular targets have been researched in lung cancer treatments and the developments in treatment modalities have been achieved. Trophoblast cell surface antigen 2 (TROP2) has recently emerged as a protein of interest with accumulating evidence regarding its prognostic and predictive significance in non-small cell lung carcinoma (NSCLC) cases. TROP2 overexpression in solid tumors has been shown as poor prognostic parameter. In this study, it is aimed to determine expression status of TROP2 antibody in NSCLC cases and to search the relationship between histopathological and clinical parameters as well as the effect on prognosis. Material and Method: This study included a total of 238 pathology specimens including 193 primary NSCLC and 45 metastasectomy cases which were evaluated at the Department of Medical Pathology in Cerrahpaşa Faculty of Medicine of Istanbul University. TROP2 antibody was performed via immunohistochemical method. Correlation between TROP2 expression and clinicopathological parameters as well as survival were analyzed. Statistical analyses were conducted using SPSS version 26.0. Results: Among the primary NSCLC cases, 43 patients (22,28%) were female while 150 (77,72%) were male. TROP2 expression was observed in 95,77% of the cases. Among these, 60,77% were adenocarcinomas, 33,15% were squamous cell carcinomas and %6,08 were in the group called "others". Cases without metastasis, TROP2 H score (p=0,027) and tumor proportion score (TPS)(p=0,041) were significantly higher. When only TROP2 expression intensities of 2+ or 3+ was considered positive, in cases lacking bronchial surgical margin positivity and distant metastasis, overall survival was reduced in cases exhibiting a TPS ≥ 20%. Even in metastasectomy cases 36 out of 45 (80%), positivity was identified. Higher TROP2 H scores were observed in metastatic squamous cell carcinoma cases, while lower scores were found in the heterogeneous "other" category including large cell neuroendocrine carcinoma, pleomorphic carcinoma, NSCLC- not otherwise specified (p=0,009). Conclusion: TROP2 expression rate is high in NSCLC. In this study, the negative effects of TROP2 positivity on overall survival is shown in cases where TROP2 expression was considered positive only at 2+ and 3+ intensity, in which bronchial surgical margin positivity and metastasis were not observed, and in cases with a total staining percentage (TPS) ≥20%. Moreover, this study demonstrates TROP2 expression not only in primary NSCLC, but also in metastatic group. Larger scale studies are needed to clearly define the prognostic and predictive roles of TROP2 in lung cancer as well as to inform its potential utility in clinical decision-making and targeted therapeutic approaches. Keywords: Non-small cell lung carcinoma, prognosis, TROP2, targeted therapies