Overexpression of trophoblast cell surface antigen 2 is associated with BRAF V600E mutation and aggressive behavior in papillary thyroid cancer.

Papillary thyroid cancer (PTC) is the most common endocrine tumor with an increasing incidence. The dilemma in treating this cancer is how to discriminate the tumors with aggressive behavior from the indolent ones. Trophoblast cell surface antigen 2 (trop-2) has been identified in multiple epithelial cancers and proven to be associated with shortened overall survival and disease-free survival. In this study, we retrospectively collected the clinicopathologic characteristics of 145 patients who underwent surgery at Fudan University Shanghai Cancer Center (FUSCC), and a validation cohort from The Cancer Genome Atlas (TCGA) database was identified to support the conclusion. Quantitative real-time polymerase chain reaction (qPCR) was employed to determine trop-2 mRNA in cancer tissue and adjacent normal tissue of PTC. BRAFV600E mutation analysis was determined using Sanger sequencing. The correlation of trop-2 and clinical characteristics was analyzed with Mann-Whitney U, Kruskal-Wallis, χ2, and Fisher's exact tests. Trop-2 overexpression was significantly associated with lymph node metastasis (LNM) (FUSCC, P<0.001; TCGA, P<0.001) and extrathyroidal extension(ETE) (FUSCC, P=0.006; TCGA, P<0.001) in both the FUSCC and TCGA cohorts. It also proved to be an independent risk factor for LNM and ETE in multivariate analysis in both cohorts. Furthermore, trop-2 expression was also associated with BRAFV600E mutation, P<0.001 in both cohorts. The study found that trop-2 overexpression was correlated with LNM and ETE. Additionally, it was associated with BRAF mutation, therefore, trop-2 overexpression was a potential biomarker for aggressive behaviors of PTC, also it could be an indication for targeted therapy.