Real-world insights into the prevalence and prognostic significance of trophoblast cell-surface antigen 2 and folate receptor alpha in uterine carcinosarcoma
Uterine carcinosarcomas (UCS) are rare and aggressive gynecological tumors and the description of biomarkers that can help guide targeted treatments in this disease is a critical gap in current medical research. This study aims to measure the prevalence of trophoblast cell-surface antigen 2 (Trop-2) and folate receptor alpha (FRα) in UCS and evaluate their prognostic significance. This retrospective analysis examined data from female patients diagnosed with UCS who underwent surgery followed by carboplatin and paclitaxel chemotherapy between January 2012 and December 2020. Tissue microarrays from 89 samples were assessed for Trop-2 and FRα expression by IHC. High positivity was defined as a score of ≥ 50% of tumor cells with strong staining intensity for Trop-2 and ≥ 75% with medium or strong staining intensity for FRα. Sociodemographic and clinical features were analyzed alongside progression-free survival (PFS) and overall survival (OS) outcomes. The mean age at diagnosis was 66.2 years (Standard Deviation, SD: 7) and the mean body mass index was 28.7 kg/m² (SD: 6.2). Non-white women accounted for 71.6% of cases. Heterologous subtype corresponded to 63.0% of cases, and lymphovascular invasion was observed in 59.2%. Complete resection (R0) was achieved in 66.3% of cases. High expression of Trop-2 and FRα was found in 49.4% and 17.4% of epithelial components, respectively, with no high positivity in sarcomatous components. Negative margins were more common in stage I/II disease (p = 0.001), and FRα overexpression correlated with Trop-2 overexpression (p = 0.007). On multivariate analysis, advanced stage (p = 0.015) and incomplete resection (p < 0.001) predicted shorter PFS, while both factors also independently worsened OS (p = 0.013 and p = 0.001, respectively). Lymphadenectomy was associated with improved OS (p = 0.025). Complete resection and advanced stage were suggested as prognostic factors in UCS. FRα and Trop-2 are increasingly recognized as therapeutic targets and their elevated expression levels in the epithelial component of UCS are promising, although not associated with prognosis in this cohort.